Nicholas Fitz, PhD

Research Assistant Professor, Environmental and Occupational Health

Contact

Public Health Building, 130 De Soto Street, Pittsburgh, PA 15261
R-znvy: assvgm@cvgg.rqh
Primary Phone: 967-179-3117
Secondary Phone: 967-838-2363
Web site:


Personal Statement

Research to characterize the Alzheimer’s Disease Exposome will address major gaps in understanding of how environmental factors interact with genetic factors to increase or reduce risk for the disease across individual age and duration of exposure. This research direction in AD is now supported by recent articles published by the Alzheimer’s Association and funding through the NIA. We know that increasing age is the most important risk factor for Alzheimer’s disease, but many other risk factors including environmental exposures are poorly understood. The importance of environmental factors in gene-environment interactions is suggested by wide individual differences in cognitive loss and pathology progression, particularly among people who carry genes that increase the risk of Alzheimer’s disease. Among carriers of APOE4, few people never develop the disease – suggesting environmental risk as contributing to that variability. A recent study showed that environmental factors including exposure to air pollution and low socioeconomic status shifted the onset by ten years in a cohort of familial Alzheimer’s disease patients. The proposed AD exposome includes macrolevel external factors such as living in rural versus urban areas, along with individual external factors such as toxicant exposures, diet, exercise and infections. These exogenous domains can overlap and interact with endogenous factors including individual fat deposits, hormones, and brain injury. One could assume that some of these endogenous factors cold result in system interactions, describing a “lung-brain axis” for inhaled neurotoxicants of air pollution and cigarette smoke, or a “renal-brain axis” for renal aging driven by diet and hypertension. To further develop an Alzheimer’s disease “roadmap” of modifiable factors in brain aging and dementia, we are exploring how the exposome, with low level arsenic exposure as a model, impacts the normal function of neurons, microglia and astrocytes through assessing changes in the cell specific epigenome, homeostatic functions, and lipid transport. We hypothesis that exposures, either during important developmental windows or during long periods of one’s life, will influence normal neural functions which could predispose to AD or accelerate the disease progression. I have a broad background in the use of transgenic animal models, transcriptomics, microscopy, molecular genetics, cellular and molecular biology, with specific training and expertise in molecular pathogenesis and experimental therapy for neurodegenerative disease and neuroinflammation.


Education

2008 | Duquesne University Mylan School of Pharmacy | PhD in Pharmacology and Toxicology
2001 | Pennsylvania State University | BS in Animal Bioscience


Teaching

ENVIRONMENTAL AND OCCUPATIONAL HEALTH SCIENCES JOURNAL CLUB


Selected Publications

Fitz NF, Nam KN, Wolfe CM, Letronne F, Playso BE, Iordanova BE, Kozai TDY, Biedrzycki RJ, Kagan VE, Tyurina YY, Han X, Lefterov I, Koldamova R. Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer's disease. Nat Commun. 2021 Jun 7;12(1):3416. doi: 10.1038/s41467-021-23762-0. PMID: 34099706; PMCID: PMC8184801.

 

Fitz NF, Wolfe CM, Playso BE, Biedrzycki RJ, Lu Y, Nam KN, Lefterov I, Koldamova R. Trem2 deficiency differentially affects phenotype and transcriptome of human APOE3 and APOE4 mice. Mol Neurodegener. 2020 Jul 23;15(1):41. doi: 10.1186/s13024-020-00394-4. PMID: 32703241; PMCID: PMC7379780.

 

Fitz NF, Tapias V, Cronican AA, Castranio EL, Saleem M, Carter AY, Lefterova M, Lefterov I, Koldamova R. Opposing effects of Apoe/Apoa1 double deletion on amyloid-β pathology and cognitive performance in APP mice. Brain. 2015 Dec;138(Pt 12):3699-715. doi: 10.1093/brain/awv293. Epub 2015 Oct 28. PMID: 26510953; PMCID: PMC4731410.

 

Fitz NF, Castranio EL, Carter AY, Kodali R, Lefterov I, Koldamova R. Improvement of memory deficits and amyloid-β clearance in aged APP23 mice treated with a combination of anti-amyloid-β antibody and LXR agonist. J Alzheimers Dis. 2014;41(2):535-49. doi: 10.3233/JAD-132789. PMID: 24643138; PMCID: PMC4346309.

 

Fitz NF, Cronican AA, Lefterov I, Koldamova R. Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models". Science. 2013 May 24;340(6135):924-c. doi: 10.1126/science.1235809. PMID: 23704552; PMCID: PMC4086452

 

Fitz NF, Cronican AA, Saleem M, Fauq AH, Chapman R, Lefterov I, Koldamova R. Abca1 deficiency affects Alzheimer's disease-like phenotype in human ApoE4 but not in ApoE3-targeted replacement mice. J Neurosci. 2012 Sep 19;32(38):13125-36. doi: 10.1523/JNEUROSCI.1937-12.2012. PMID: 22993429; PMCID: PMC3646580.

 

Fitz NF, Cronican A, Pham T, Fogg A, Fauq AH, Chapman R, Lefterov I, Koldamova R. Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. J Neurosci. 2010 May 19;30(20):6862-72. doi: 10.1523/JNEUROSCI.1051-10.2010. PMID: 20484628; PMCID: PMC2883862.

Nicholas  Fitz