Lilian Calderon-Garciduenas

Professor

Contact Information

Department:
Bmed Acf
Email:
lilian.calderon-garciduenas@umontana.edu
Phone:
(406) 243-4785
Office Hours:

By Appointment

Office Address

Bmed Acf
SKAGGS 287
32 Campus Dr MS 1552
Missoula MT, 59812

WELCOME TO THE

ENVIRONMENTAL NEUROPREVENTION LABORATORY

Lilian Calderón-Garcidueñas MA,MD,PhD

If you are interested in Dr. Calderón talking to your group about Air pollution, Alzheimer and Parkinson's diseases, please contact us. Tax-deductible donations are welcome! Numerous collaborators and students have contributed breakthrough discoveries in neuroscience and links to this site we hope will help you to understand what makes our laboratory an exciting place to work, learn, and teach. Explore and enjoy!

Primary Investigator                                                                                        Contact

                                                                                          E mail: lilian.calderon-garciduenas@umontana.edu

                                                                                          Phone: 406-243-478

                                                                             Address: 32 Campus Drive, 287 Skaggs Bldg.,                Missoula, MT, 59812, USA

             

                                                      

 

About:

     Lilian Calderón-Garcidueñas grew-up is a small Gulf of Mexico town, the oldest daughter of two young physicians, she was raised in a nurturing environment where the daily contact with patients was the rule and over dinner conversations were delightful ways to start her in medical and literature subjects, two main interest of her parents. She knew she wanted to be a physician by the time she finished middle school and she started medical school at age 15.  The following year, she was the TA’s to the Chair of Embryology at the National University Medical School in Mexico City and started her life-long passion for teaching. Her first day as a TA’s in medical school surrounded by ~40 much older first year students,  she was told she was in the wrong place, the middle school was 3 blocks away. Her love for exploring disease causes started in medical school and she decided to pursue her studies in the USA and Canada. Her pathology and neuropathology training at the University of Toronto were followed by her fellowship at Harvard University and her first position as an Assistant professor at Northwestern University in Chicago. She earned an American Board in Anatomical Pathology and Neuropathology in 1981. Literature was always in her mind, so she went back to school and earned a BS in English Literature and a MA in Comparative Literature in 1997. Her interest for clinical environmental research took her back to Chapel Hill, North Carolina where she earned a PhD in Toxicology in 2001, followed by three years as a postdoctoral fellow in Environmental Pathology.  She loves her work, her teaching is key to her way to transmit her contagious enthusiasm for medicine, science and her research work and in her free time she paints, cooks and tenders her vegetable garden and cooks some more. Her husband is a UM 2011 graduate with a PhD in History and with two children also UM alumni, her house is surrounded by grizzly memorabilia.

Courses Taught

USE AND ABUSE OF DRUGS SPRING AND WINTER

Teaching Experience

I have been teaching in medical schools since I was 16y old and I truly enjoy sharing with our young students the amazing world of neuroresearch .

I love giving Seminars and doing students presentations with subjects of their interest.

Research Interests

Alzheimer's, Parkinson's and TDP-43 diseases in children and young adults with high exposures to combustion and industrial particulate matter (including FOREST FIRES).

Neuroprotection is a health urgent need. We have no support to do studies.

Projects

DONATIONS TO THE ENVIRONMENTAL NEUROPREVENTION LABORATORY

Donors can make checks out to the UM Foundation with a notation for the Environmental Neuroprevention Laboratory:

UM Foundation

PO Box 7159

Missoula, MT 59807 USA

Donors can give online at www.supportum.org/give

In the section “Choose a designation” please select “Other” and then type Environ Neuroprev Lab in the Comments section.

Thank you!!!!!!!!!!!!!!!!!!

Field of Study

Our laboratory is focused on studying the early development of neurodegenerative changes in the brains of children and young adults residing in polluted cities. Neuroprotection is our GOAL.

ALZHEIMER DISEASE, PARKINSON DISEASE AND TDP-43 PATHOLOGY START IN PEDIATRIC AGES IN HIGHLY EXPOSED URBANITES.

Exposures to sustained high concentrations of fine particulate matter PM2.5 and combustion and industrial NANOPARTICLES  are risk factors for neurodegenerative FATAL diseases.

We have reported the development and progression of AD, PD and TDP-43 pathology in 203 forensic autopsies from Metropolitan Mexico City in subjects aged 11 months to 40y. 202/203 autopsies have the ALZHEIMER hallmarks, 23% Parkinson and 18% TDP-43 pathology. Children and young Mexico City adults have significant cognitive deficits starting in pediatric ages and progressing as the subjects grow up in the city.Gait and equilibrium and BAEPs abnormalities plus brain structural and metabolic changes are present. Young adults have significant frontal and temporal, caudate and cerebellar atrophy. We are deeply concerned about APOE4 children and young adults with higher risk for suicide associated to acceleration of neurofibrillary tangle stages.Nanoparticles reach the fetal brain and cross the placenta at all stages of development.

ALZHEIMER STARTS IN PEDIATRIC AGES IN POLLUTED ENVIRONMENTS.

Part 1: https://www.youtube.com/watch?v=7jdVjWK0u9Q

 Part 2: https://www.youtube.com/watch?v=D2ys4bKNEGQ

 Part 3: https://www.youtube.com/watch?v=EX_FLc6NXDg

 

Selected Publications

Please read them 

Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders-Denial is not an option.

Calderón-Garcidueñas L, Torres-Jardón R, Greenough GP, Kulesza R, González-Maciel A, Reynoso-Robles R, García-Alonso G, Chávez-Franco DA, García-Rojas E, Brito-Aguilar R, Silva-Pereyra HG, Ayala A, Stommel EW, Mukherjee PS.Front Neurol. 2023 Feb 27;14:1117695. doi: 10.3389/fneur.2023.1117695. Free PMC article. 

 

Fall Risk, Sleep Behavior, and Sleep-Related Movement Disorders in Young Urbanites Exposed to Air Pollution.

Calderón-Garcidueñas L, Kulesza R, Greenough GP, García-Rojas E, Revueltas-Ficachi P, Rico-Villanueva A, Flores-Vázquez JO, Brito-Aguilar R, Ramírez-Sánchez S, Vacaseydel-Aceves N, Cortes-Flores AP, Mansour Y, Torres-Jardón R, Villarreal-Ríos R, Koseoglu E, Stommel EW, Mukherjee PS.J Alzheimers Dis. 2023;91(2):847-862. doi: 10.3233/JAD-220850.

 

TDP-43 CSF Concentrations Increase Exponentially with Age in Metropolitan Mexico City Young Urbanites Highly Exposed to PM2.5 and Ultrafine Particles and Historically Showing Alzheimer and Parkinson's Hallmarks. Brain TDP-43 Pathology in MMC Residents Is Associated with High Cisternal CSF TDP-43 Concentrations.

Calderón-Garcidueñas L, Stommel EW, Lachmann I, Waniek K, Chao CK, González-Maciel A, García-Rojas E, Torres-Jardón R, Delgado-Chávez R, Mukherjee PS.Toxics. 2022 Sep 24;10(10):559. doi: 10.3390/toxics10100559.PMID: 36287840 Free PMC article.

 

Air Pollution, Ultrafine Particles, and Your Brain: Are Combustion Nanoparticle Emissions and Engineered Nanoparticles Causing Preventable Fatal Neurodegenerative Diseases and Common Neuropsychiatric Outcomes?

Calderón-Garcidueñas L, Ayala A.Environ Sci Technol. 2022 Jun 7;56(11):6847-6856. doi: 10.1021/acs.est.1c04706. Free article. 

 

Common Fatal Neurodegenerative Diseases Revisited: Beyond Age, Comorbidities, and Devastating Terminal Neuropathology There Is Hope With Prevention.

Calderón-Garcidueñas L.Front Neurol. 2022 May 11;13:901447. doi: 10.3389/fneur.2022.901447. PMID: 35645968 Free PMC article. 

 

A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk.

Re DB, Yan B, Calderón-Garcidueñas L, Andrew AS, Tischbein M, Stommel EW.J Neurol. 2022 May;269(5):2359-2377. doi: 10.1007/s00415-021-10928-5.

 

Environmentally Toxic Solid Nanoparticles in Noradrenergic and Dopaminergic Nuclei and Cerebellum of Metropolitan Mexico City Children and Young Adults with Neural Quadruple Misfolded Protein Pathologies and High Exposures to Nano Particulate Matter.

Calderón-Garcidueñas L, González-Maciel A, Reynoso-Robles R, Silva-Pereyra HG, Torres-Jardón R, Brito-Aguilar R, Ayala A, Stommel EW, Delgado-Chávez R.Toxics. 2022 Mar 29;10(4):164. doi: 10.3390/toxics10040164.PMID: 35448425 Free PMC article.

 

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution.

Calderón-Garcidueñas L, Hernández-Luna J, Mukherjee PS, Styner M, Chávez-Franco DA, Luévano-Castro SC, Crespo-Cortés CN, Stommel EW, Torres-Jardón R.Toxics. 2022 Mar 25;10(4):156. doi: 10.3390/toxics10040156.PMID: 35448417 Free PMC article.

 

Environmental Nanoparticles Reach Human Fetal Brains.

Calderón-Garcidueñas L, Pérez-Calatayud ÁA, González-Maciel A, Reynoso-Robles R, Silva-Pereyra HG, Ramos-Morales A, Torres-Jardón R, Soberanes-Cerino CJ, Carrillo-Esper R, Briones-Garduño JC, Conde-Gutiérrez YDS.Biomedicines. 2022 Feb 9;10(2):410. doi: 10.3390/biomedicines10020410.PMID: 35203619 Free PMC article. 

 

Metals, Nanoparticles, Particulate Matter, and Cognitive Decline.

Calderón-Garcidueñas L, Chávez-Franco DA, Luévano-Castro SC, Macías-Escobedo E, Hernández-Castillo A, Carlos-Hernández E, Franco-Ortíz A, Castro-Romero SP, Cortés-Flores M, Crespo-Cortés CN, Torres-Jardón R, Stommel EW, Rajkumar RP, Mukherjee PS; Research Universidad del Valle de México UVM Group.Front Neurol. 2022 Jan 21;12:794071. doi: 10.3389/fneur.2021.794071.

 

Particulate Air Pollution and Risk of Neuropsychiatric Outcomes. What We Breathe, Swallow, and Put on Our Skin Matters.

Calderón-Garcidueñas L, Stommel EW, Rajkumar RP, Mukherjee PS, Ayala A.Int J Environ Res Public Health. 2021 Nov 3;18(21):11568. doi: 10.3390/ijerph182111568.PMID: 34770082 Free PMC article. 

Parkinson disease and air pollution: does what we breathe matter? Calderón-Garcidueñas L. Nat Rev Neurol. 2021 Aug;17(8):467-468. doi: 10.1038/s41582-021-00531-7.

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders.

Calderón-Garcidueñas L, Rajkumar RP, Stommel EW, Kulesza R, Mansour Y, Rico-Villanueva A, Flores-Vázquez JO, Brito-Aguilar R, Ramírez-Sánchez S, García-Alonso G, Chávez-Franco DA, Luévano-Castro SC, García-Rojas E, Revueltas-Ficachi P, Villarreal-Ríos R, Mukherjee PS. Int J Environ Res Public Health. 2021 Jun 22;18(13):6689. doi: 10.3390/ijerph18136689
Environmental Fe, Ti, Al, Cu, Hg, Bi, and Si Nanoparticles in the Atrioventricular Conduction Axis and the Associated Ultrastructural Damage in Young Urbanites: Cardiac Arrhythmias Caused by Anthropogenic, Industrial, E-Waste, and Indoor Nanoparticles.
Calderón-Garcidueñas L, González-Maciel A, Reynoso-Robles R, Rodríguez-López JL, Silva-Pereyra HG, Labrada-Delgado GJ, Pérez-Guillé B, Soriano-Rosales RE, Jiménez-Bravo Luna MA, Brito-Aguilar R, Mukherjee PS, Gayosso-Chávez C, Delgado-Chávez R. Environ Sci Technol. 2021 Jun 15;55(12):8203-8214.
Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young.
Calderón-Garcidueñas L, Torres-Solorio AK, Kulesza RJ, Torres-Jardón R, González-González LO, García-Arreola B, Chávez-Franco DA, Luévano-Castro SC, Hernández-Castillo A, Carlos-Hernández E, Solorio-López E, Crespo-Cortés CN, García-Rojas E, Mukherjee PS; Research Universidad del Valle de México UVM Group. Environ Res. 2020 Dec;191:110087. doi: 10.1016/j.envres.2020.110087.

Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal.

Calderón-Garcidueñas L, González-Maciel A, Reynoso-Robles R, Hammond J, Kulesza R, Lachmann I, Torres-Jardón R, Mukherjee PS, Maher BA. Environ Res. 2020 Dec;191:110139. doi: 10.1016/j.envres.2020.110139.
 

Iron-rich air pollution nanoparticles: An unrecognised environmental risk factor for myocardial mitochondrial dysfunction and cardiac oxidative stress. Maher BA, González-Maciel A, Reynoso-Robles R, Torres-Jardón R, Calderón-Garcidueñas L. Environ Res. 2020 Sep;188:109816. doi: 10.1016/j.envres.2020.109816.

Reduced repressive epigenetic marks, increased DNA damage and Alzheimer's disease hallmarks in the brain of humans and mice exposed to particulate urban air pollution.

Calderón-Garcidueñas L, Herrera-Soto A, Jury N, Maher BA, González-Maciel A, Reynoso-Robles R, Ruiz-Rudolph P, van Zundert B, Varela-Nallar L. Environ Res. 2020 Apr;183:109226. doi: 10.1016/j.envres.2020.109226.
Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress.
Calderón-Garcidueñas L, Torres-Jardón R, Kulesza RJ, Mansour Y, González-González LO, Gónzalez-Maciel A, Reynoso-Robles R, Mukherjee PS. Environ Res. 2020 Apr;183:109137. doi: 10.1016/j.envres.2020.109137.
 

Environmental Nanoparticles, SARS-CoV-2 Brain Involvement, and Potential Acceleration of Alzheimer's and Parkinson's Diseases in Young Urbanites Exposed to Air Pollution. Calderón-Garcidueñas L, Torres-Jardón R, Franco-Lira M, Kulesza R, González-Maciel A, Reynoso-Robles R, Brito-Aguilar R, García-Arreola B, Revueltas-Ficachi P, Barrera-Velázquez JA, García-Alonso G, García-Rojas E, Mukherjee PS, Delgado-Chávez R. J Alzheimers Dis. 2020;78(2):479-503.

Combustion- and friction-derived magnetic air pollution nanoparticles in human hearts.

Calderón-Garcidueñas L, González-Maciel A, Mukherjee PS, Reynoso-Robles R, Pérez-Guillé B, Gayosso-Chávez C, Torres-Jardón R, Cross JV, Ahmed IAM, Karloukovski VV, Maher BA. Environ Res. 2019 Sep;176:108567. doi: 10.1016/j.envres.2019.108567.

Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology.Calderón-Garcidueñas L, González-Maciel A, Reynoso-Robles R, Kulesza RJ, Mukherjee PS, Torres-Jardón R, Rönkkö T, Doty RL.

Environ Res. 2018 Oct;166:348-362. doi: 10.1016/j.envres.2018.06.027. Epub 2018 Jun 20.

Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. APOE4 carriers have higher suicide risk and higher odds of reaching NFT stage V at ≤ 40 years of age.Calderón-Garcidueñas L, Gónzalez-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Mukherjee PS, Kulesza RJ, Torres-Jardón R, Ávila-Ramírez J, Villarreal-Ríos R.Environ Res. 2018 Jul;164:475-487. doi: 10.1016/j.envres.2018.03.023. Epub 2018 Mar 26.

Combustion-derived nanoparticles, the neuroenteric system, cervical vagus, hyperphosphorylated alpha synuclein and tau in young Mexico City residents.

Calderón-Garcidueñas L, Reynoso-Robles R, Pérez-Guillé B, Mukherjee PS, Gónzalez-Maciel A.Environ Res. 2017 Nov;159:186-201. doi: 10.1016/j.envres.2017.08.008. Epub 2017 Aug 10.
Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.Calderón-Garcidueñas L, González-González LO, Kulesza RJ, Fech TM, Pérez-Guillé G, Luna MAJ, Soriano-Rosales RE, Solorio E, Miramontes-Higuera JJ, Gómez-Maqueo Chew A, Bernal-Morúa AF, Mukherjee PS, Torres-Jardón R, Mills PC, Wilson WJ, Pérez-Guillé B, D'Angiulli A.Environ Res. 2017 Oct;158:324-332. doi: 10.1016/j.envres.2017.06.026. Epub 2017 Jun 30.

Characterization of the superior olivary complex of Canis lupus domesticus.Fech T, Calderón-Garcidueñas L, Kulesza RJ Jr.Hear Res. 2017 Aug;351:130-140. doi: 10.1016/j.heares.2017.06.010. Epub 2017 Jun 15.

Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer's Disease Development.

González-Maciel A, Reynoso-Robles R, Torres-Jardón R, Mukherjee PS, Calderón-Garcidueñas L.J Alzheimers Dis. 2017;59(1):189-208. doi: 10.3233/JAD-170012.

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer's Disease Development in Mexico City Young Females.Calderón-Garcidueñas L, de la Monte SM.J Alzheimers Dis. 2017;58(3):613-630. doi: 10.3233/JAD-161299. Review.

Living close to heavy traffic roads, air pollution, and dementia.Calderón-Garcidueñas L, Villarreal-Ríos R.Lancet. 2017 Feb 18;389(10070):675-677. doi: 10.1016/S0140-6736(16)32596-X. Epub 2017 Jan 5.

Identification of aberrant white matter bundles entering the inferior cerebellar peduncle.Blackburn K, LeMay J, Dale G, Calderón-Garcidueñas L, Kulesza R Jr.Neurology. 2017 Jan 3;88(1):106-107.

Magnetite pollution nanoparticles in the human brain.Maher BA, Ahmed IA, Karloukovski V, MacLaren DA, Foulds PG, Allsop D, Mann DM, Torres-Jardón R, Calderon-Garciduenas L.

Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):10797-801. doi: 10.1073/pnas.1605941113. Epub 2016 Sep 6.

Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.

Calderón-Garcidueñas L, Avila-Ramírez J, Calderón-Garcidueñas A, González-Heredia T, Acuña-Ayala H, Chao CK, Thompson C, Ruiz-Ramos R, Cortés-González V, Martínez-Martínez L, García-Pérez MA, Reis J, Mukherjee PS, Torres-Jardón R, Lachmann I.J Alzheimers Dis. 2016 Sep 6;54(2):597-613. doi: 10.3233/JAD-160472.
Chocolate, Air Pollution and Children's Neuroprotection: What Cognition Tools should be at Hand to Evaluate Interventions? Calderón-Garcidueñas L, San Juan Chávez V, Vacaseydel-Aceves NB, Calderón-Sánchez R, Macías-Escobedo E, Frías C, Giacometto M, Velasquez L, Félix-Villarreal R, Martin JD, Draheim C, Engle RW.Front Pharmacol. 2016 Aug 11;7:232. doi: 10.3389/fphar.2016.00232. eCollection 2016. Review.

Smoking and Cerebral Oxidative Stress and Air Pollution: A Dreadful Equation with Particulate Matter Involved and One More Powerful Reason Not to Smoke Anything!

Calderón-Garcidueñas L.J Alzheimers Dis. 2016 Jul 22;54(1):109-12. doi: 10.3233/JAD-160510.
Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City.Calderón-Garcidueñas L, Jewells V, Galaz-Montoya C, van Zundert B, Pérez-Calatayud A, Ascencio-Ferrel E, Valencia-Salazar G, Sandoval-Cano M, Carlos E, Solorio E, Acuña-Ayala H, Torres-Jardón R, D'Angiulli A.Environ Res. 2016 Oct;150:411-22. doi: 10.1016/j.envres.2016.06.026. Epub 2016 Jul 2.

Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease.Calderón-Garcidueñas L, Reynoso-Robles R, Vargas-Martínez J, Gómez-Maqueo-Chew A, Pérez-Guillé B, Mukherjee PS, Torres-Jardón R, Perry G, Gónzalez-Maciel A.

Environ Res. 2016 Apr;146:404-17. doi: 10.1016/j.envres.2015.12.031. Epub 2016 Jan 30.
Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond.

Calderón-Garcidueñas L, Leray E, Heydarpour P, Torres-Jardón R, Reis J.Rev Neurol (Paris). 2016 Jan;172(1):69-80. doi: 10.1016/j.neurol.2015.10.008. Epub 2015 Dec 21. Review.

A Critical Proton MR Spectroscopy Marker of Alzheimer's Disease Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE É›4 Mexico City Children and Their Parents.Calderón-Garcidueñas L, Mora-Tiscareño A, Melo-Sánchez G, Rodríguez-Díaz J, Torres-Jardón R, Styner M, Mukherjee PS, Lin W, Jewells V.

J Alzheimers Dis. 2015;48(4):1065-75. doi: 10.3233/JAD-150415.

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.Calderón-Garcidueñas L, Franco-Lira M, D'Angiulli A, Rodríguez-Díaz J, Blaurock-Busch E, Busch Y, Chao CK, Thompson C, Mukherjee PS, Torres-Jardón R, Perry G.Environ Res. 2015 Jul;140:579-92. doi: 10.1016/j.envres.2015.05.012. Epub 2015 Jun 1.

Urban air pollution, poverty, violence and health--Neurological and immunological aspects as mediating factors. Kristiansson M, Sörman K, Tekwe C, Calderón-Garcidueñas L.

Environ Res. 2015 Jul;140:511-3. doi: 10.1016/j.envres.2015.05.013. Epub 2015 May 22.

Publications

â—™ Neuroprevention of the two major neurodegenerative diseases affecting our populations: Alzheimer and Parkinson’s diseases

â—™ The role of air pollutants in the development of neuroinflammation and neurodegeneration in children and teens.

â—™ Educate the public and our students on the latest scientific discoveries about the brain, and how these discoveries are relevant in our daily lives and well-being.

 

Researchers share their passion for science (please go to the link KPAX TV video)

http://www.kpax.com/news/um-study-looks-at-how-air-pollution-and-effects-young-brains/

 

Area of Research

My research is deeply interdisciplinary as it covers pathology, neuropathology, environmental toxicology, pediatrics, neurology, psychiatry, atmospheric chemistry, cognitive neuropsychology, developmental science, sociology of education, and educational psychology. In spite of the evident eclecticism, the scientific questions I am after pertain to fundamental issues in how the environment impacts people’s health. More specifically, I have been working on the effects of air pollutants such as particulate matter (PM) upon the brain in development.

We live in complex environments surrounded by mostly hidden chemical, biological and physical hazards. Our central mission is to work with a community of multidisciplinary researchers interested in the mechanisms of environmentally-induced diseases, in solving the problems facing our vulnerable populations, and in implementing an integrative approach to human environmental disease.

Research links air pollution mostly to respiratory and cardiovascular disease. The effects of air pollution on the central nervous system (CNS) are not broadly recognized. Urban outdoor pollution is a global public health problem particularly severe in megacities and in underdeveloped countries, but large and small cities in the United States, Canada and Mexico and across the world are not spared. Fine and ultrafine particulate matter (UFPM) defined by aerodynamic diameter (<2.5-μm fine particles, PM2.5, and <100-nm UFPM) pose a special interest for the brain effects given the capability of very small particles to reach the brain.

In adults, ambient pollution is associated to stroke, depression and suicide, whereas the emerging picture in children show significant systemic inflammation, immunodysregulation at systemic, intratechal and brain levels, neuroinflammation and brain oxidative stress, along with the main hallmarks of Alzheimer and Parkinson's diseases: hyperphosphorilated tau, amyloid plaques and misfolded α-synuclein.

The applied spin of my research has been on the cognitive and structural detrimental brain impact of air pollutants upon healthy children. How specific air pollutants reach the brain and start a cascade of events producing significant inflammation and changes in proteins that are key players in Alzheimer and Parkinson’s diseases? How a seemingly healthy child can lost >10 point in their IQ for living in a polluted city?

Pediatric air pollution research requires extensive multidisciplinary collaborations to accomplish a critical goal: to protect exposed children through multidimensional interventions having both broad impact and reach. Protecting children and teens from neural effects of air pollution should be of pressing importance for public health and we need your support.

My research contributions can be subdivided in the following five areas (for each area, a representative publication is indicated):

1.Making the link between air pollution exposures and the development of Alzheimer and Parkinson’s diseases in childhood and young adults.

Children residents in large cities exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. The accumulation of misfolded proteins in exposed children coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau , alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. We favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children.

ALZHEIMER AND PARKINSON'S DISEASES START IN CHILDHOOD IN HIGHLY POLLUTED CITIES:

Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. APOE4 carriers have higher suicide risk and higher odds of reaching NFT stage V at ≤ 40 years of age.Calderón-Garcidueñas L, Gónzalez-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Mukherjee PS, Kulesza RJ, Torres-Jardón R, Ávila-Ramírez J, Villarreal-Ríos R.Environ Res. 2018 Jul;164:475-487. doi: 10.1016/j.envres.2018.03.023. Epub 2018 Mar 26.

Early Alzheimer's and Parkinson's disease pathology in urban children: Friend versus Foe responses--it is time to face the evidence.Calderón-Garcidueñas L, Franco-Lira M, Mora-Tiscareño A, Medina-Cortina H, Torres-Jardón R, Kavanaugh M.Biomed Res Int. 2013;2013:161687.

Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.Calderón-Garcidueñas L, Kavanaugh M, Block M, D'Angiulli A, Delgado-Chávez R, Torres-Jardón R, González-Maciel A, Reynoso-Robles R, Osnaya N, Villarreal-Calderon R, Guo R, Hua Z, Zhu H, Perry G, Diaz P.J Alzheimers Dis. 2012;28(1):93-107

Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.Calderón-Garcidueñas L, Solt AC, Henríquez-Roldán C, Torres-Jardón R, Nuse B, Herritt L, Villarreal-Calderón R, Osnaya N, Stone I, García R, Brooks DM, González-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Reed W.Toxicol Pathol. 2008 Feb;36(2):289-310.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.Calderón-Garcidueñas L, Reed W, Maronpot RR, Henríquez-Roldán C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, Aragón-Flores M, Solt AC, Altenburg M, Torres-Jardón R, Swenberg JA.Toxicol Pathol. 2004 Nov-Dec;32(6):650-8.

Air pollution and brain damage.Calderón-Garcidueñas L, Azzarelli B, Acuna H, Garcia R, Gambling TM, Osnaya N, Monroy S, DEL Tizapantzi MR, Carson JL, Villarreal-Calderon A, Rewcastle B.Toxicol Pathol. 2002 May-Jun;30(3):373-89.

 

2. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks, white matter lesions and volumetric brain changes by MRI.

These very important findings explain many parents concerns regarding school performance and behavior in their otherwise healthy children. The effects of tiny particles on the developing brain translate in brain inflammation and structural alterations in key areas in their brain, i.e., the prefrontal cortex. We have shown brain responses to air pollution vary from child to child, while some produce certain types of proteins associated with neuroprotection, others have pro-inflammatory defensive responses that do not help in terms of cognition,nor in changes in brain volumes related to their age. Identification of biomarkers associating systemic inflammation to brain growth is critical for detecting children at higher risk for cognitive deficits and neurodegeneration, thereby warranting early implementation of neuroprotective measures.

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

Calderón-Garcidueñas L, Mora-Tiscareño A, et al., Brain Cogn. 2008 Nov;68(2):117-27.

White matter hyperintensities, systemic inflammation, brain growth, and cognitive functions in children exposed to air pollution.

Calderón-Garcidueñas L1, Mora-Tiscareño A, Styner M, Gómez-Garza G, Zhu H, Torres-Jardón R, Carlos E, Solorio-López E, Medina-Cortina H, Kavanaugh M, D'Angiulli A. J Alzheimers Dis. 2012;31(1):183-91. doi: 10.3233/JAD-2012-120610.

3. Loss of smell i.e., the capacity to detect odors is an important early symptom of both Alzheimer and Parkinson’s diseases, present long before dementia or tremor.

Olfactory dysfunction influences nutrition, energy balance, enjoyment of food and their well-being under life threatening situations, including accidental gas poisonings. It is now apparent that the olfactory system undergoes neuropathological changes, neuroinflammation, DNA damage and accumulation of combustion-associated metals early in life in association with high levels of air pollution exposures.  It is also very important to know that people carrying the allele 4 of the Apolipoprotein E gene-the major genetic risk factor for Alzheimer’s disease-have early and more severe odor deficits if they live in polluted areas. Identification of vulnerable populations is important in order to protect them.

Urban air pollution: influences on olfactory function and pathology in exposed children and young adults.Calderón-Garcidueñas L, Franco-Lira M, Henríquez-Roldán C, Osnaya N, González-Maciel A, Reynoso-Robles R, Villarreal-Calderon R, Herritt L, Brooks D, Keefe S, Palacios-Moreno J, Villarreal-Calderon R, Torres-Jardón R, Medina-Cortina H, Delgado-Chávez R, Aiello-Mora M, Maronpot RR, Doty RL.Exp Toxicol Pathol. 2010 Jan;62(1):91-102.

4. The question to answer is: How can we protect children and young adults from the negative brain effects of air pollutants?

We are working on regular, available foods that will decrease inflammation, one of the key negative systemic and brain effects of air pollution. Cocoa and dark chocolate have been used in our laboratory to decrease brain inflammation with excellent results. In mice exposed to air pollution, dark chocolate (60% cacao) markedly decreased inflammation precisely in an area involved in Parkinson’s disease. In children, 30g of cocoa at breakfast time improved their memory and decreased a very powerful protein that reduces the lumen of blood vessels (vasoconstrictor).

Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children.Calderón-Garcidueñas L1, Mora-Tiscareño A, Franco-Lira M, Cross JV, Engle R, Aragón-Flores M, Gómez-Garza G, Jewells V, Medina-Cortina H, Solorio E, Chao CK, Zhu H, Mukherjee PS, Ferreira-Azevedo L, Torres-Jardón R, D'Angiulli A. Front Pharmacol. 2013 Aug 22;4:104. doi: 10.3389/fphar.2013.00104.

Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection. Villarreal-Calderon R, Torres-Jardón R, Palacios-Moreno J, Osnaya N, Pérez-Guillé B, Maronpot RR, Reed W, Zhu H, Calderón-Garcidueñas L. Int J Toxicol. 2010 Dec;29(6):604-15.

5. Obesity, insulin resistance, metabolic syndrome, cardiovascular disease and dementia.

Obesity is increasing in our populations, an ominous predictor of increases in metabolic syndrome, type 2 diabetes, cardiovascular disease and dementia. The problem is certainly a deep concern in socioeconomic disadvantage populations.

We need to look at the links between body mass index (BMI) and dementia because we can do something about the subject.  As physicians, we are very aware of the value of preventive medicine, starting in childhood and educating children and their parents about food and exercise is imperative.

6.Sleep disorders in people exposed to air pollutants

This is a fascinating area of research, the brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority. Frontiers in Neurology 2023;14:1117695

 

We have a 50 year window of opportunity between urban children and young adults have the cognitive and metabolic detrimental effects we are describing in our laboratory, and they will present with mild cognitive impairment and dementia. APOE 4, the most prevalent genetic risk factor for AD has been understudied. Facing the current pediatric clinical and imaging evidence in highly exposed children is imperative if we are aiming our efforts to identify and mitigate environmental factors influencing Alzheimer’s disease.

 

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Professional Experience

As a physician with extensive training in Anatomical Pathology and Neuropathology and then a PhD at UNC in Toxicology with a PostDoc in Environmental Pathology at UNC I am  working in the mechanistics pathways associated with nanoparticles that explain why we have extensive Alzheimer neuropathologt changes in children and young adults in Mexico City.

When 202/203 forensic autopsies between 11 months and 40y of age subjects have the Alzheimer hallmarks in their brains, we ought to know we are facing a extremely serious health crisis.

We have been talking about the subject since 2004 and the unfortunate thing is that there is no interest in doing PREVENTIVE MEDICINE. None of the medications available to date for Alzheimer is useful and so knowing the nanoparticles are damaging brains from in utero exposures of mothers to air pollution obligates us as physicians to implement preventive measures from conception. We need support to doing our research, please donate to the University of Montana Neuroprevention Laboratory, every dollar counts and is deeply appreciate it!

Calderón-Garcidueñas L, Reed W, Maronpot RR, et al..Toxicol Pathol. 2004 Nov-Dec;32(6):650-8. doi: 10.1080/01926230490520232

 

Lilian Calderon-Garciduenas

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