Ph.D., Neurobiology and Behavior. State University of New York at Stony Brook, Stony Brook, 1999
Assistant Professor of Biological Science
Apolipoprotein-E (apoE) is implicated in atherosclerosis and several other lipid-related disorders. It also affects pathogenesis in Alzheimer Disease, Multiple Sclerosis, and a few other neurological, neurodegenerative and ocular disorders. One likely reason for such far-reaching effects is that the primary role of apoE is to transport lipids within cells, organs and throughout the body. Research in the lab focuses on two aspects of apoE biology. First project involves identification of molecular mechanisms regulating apoE gene expression.
The second project involves identification of pathways by which apoE could regulate Alzheimer Disease pathogenesis. ApoE gene regulation Epidemiological studies suggest that apoE polymorphism could accelerate or delay the onset of Alzheimer Disease by more than ten years. Complete lack of apoE (knock-out mice) results in abolition of AD-like pathology in double-transgenic mice. However, the effect is quite the opposite from atherosclerosis viewpoint: Deletion of apoE results in accentuation of atherosclerotic plaques. Furthermore, mice heterozygous for apoE (+/-) are also at greater risk for atherosclerosis compared to wild-type mice. This suggests that increasing apoE expression outside the brain could have therapeutic significance for atherosclerosis, while selectively reducing apoE expression inside the brain could be beneficial in Alzheimer Disease. The goal of this project is to identify novel molecular mechanisms that can modulate apoE gene expression.
Role of apoE in Alzheimer Disease Alzheimer Disease is a neurodegenerative disease affecting more than 20% of the senior citizens above the age of 75. Neurodegeneration in AD is likely to occur due to long-term exposure to the constitutively produced Abeta neurotoxin as well as other neuronal-insults. ApoE plays a complex role in pathogenesis of AD. ApoE’s primary role is to provide cholesterol and lipids to neurons and new or regenerating synapses. It also clears Abeta from the brain by transporting it to the vasculature. However, abnormalities in this pathway can lead to aggregation of apoE with Abeta in senile plaques. The aim of this study is to identify how apoE modulates Alzheimer Disease pathology.
Patel NV, Gordon MN, Connor KE, Good RA, Engelman RW, Mason J, Morgan DG, Morgan TE, Finch CE (2005) Caloric Restriction Slows Amyloid Accumulation in Transgenic Models of Alzheimer Disease. Neurobiology of Aging, 26: 995-1000.
Wong AM, Patel NV, Patel NK, Wei M, Morgan TE, de Beer MC, de Villiers WJ, Finch CE. (2005) Macrosialin increases during normal brain aging are attenuated by caloric restriction. Neuroscience Letters, 390: 76-80.
Patel NV, Wei M, Wong AM, Morgan TE, Finch CE (2004) Aging decreases glia-derived apolipoprotein-E and J secretion. Neuroscience Letters, 371:199-204. Patel NV, Forman BM (2004) Linking lipids, Alzheimer’s & LXRs? NURSA e-Journal, 2(10): ID# 3.03082004.1.
Patel NV, Finch CE (2002) The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiology of Aging, 23:707-717.
Hitzemann R, Demarest K, Koyner J, Cipp L, Patel N, Rasmussen E, McCaughran J (2000) Effect of genetic cross on the detection of quantitative trait loci and a novel approach to mapping QTLs. Pharmacology, Biochemistry and Behavior, 67:767-772
Patel NV, Hitzemann R (1999) Detection and mapping of quantitative trait loci for haloperidol-induced catalepsy in a C57BL/6J x DBA/2J F2 intercross. Behavior Genetics, 29:303-10.
Patel N, Hitzemann B, Hitzemann R (1998) Genetics, Haloperidol, and the Fos response in the basal ganglia: A comparison of the C57BL/6J and DBA/2J inbred mouse strains. Neuropsychopharmacology, 18:480-491
Program Director, California Institute for Regenerative Medicine (CIRM) Stem Cell Research Grant, $1,280,000