Abstract

This pilot project proposes to study human brain synaptosomal heparan sulfate proteoglycan (HSPG) and its possible role in the pathogenesis of senile dementia of the Alzheimer's type (SDAT). HSPG plays an important role in normal neuronal function, and alterations in neuronal HSPG may occur with aging and be involved in the pathogenesis of SDAT. Of interest, recent data suggest that the amyloid found in SDAT is identical to a species of HSPG derived from a rat neuronal cell line. To our knowledge neuronal HSPG has not been isolated from human brain. The ADRC provides a unique opportunity to conduct studies on human brain synaptosomal HSPG from both normal individuals and patients with SDAT. We will attempt to demonstrate the presence of alterations in human brain synaptosomal HSPG in SDAT and the immunochemical and biochemical relationship between that HSPG and beta-amyloid. The proposed studies should contribute to our understanding of the nature of human brain synaptosomal HSPG in normal aging and SDAT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
2P50AG005138-06
Application #
3813968
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N et al. (2018) Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359:693-697
Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416
Huckins, L M; Hatzikotoulas, K; Southam, L et al. (2018) Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Mol Psychiatry 23:1169-1180
Soleimani, Laili; Ravona-Springer, Ramit; Heymann, Anthony et al. (2018) Depression is more strongly associated with cognition in elderly women than men with type 2 diabetes. Int Psychogeriatr :1-5
Ki?emet-Piska?, Spomenka; Babi? Leko, Mirjana; Blažekovi?, Antonela et al. (2018) Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia. CNS Neurosci Ther 24:734-740
Audrain, Mickael; Haure-Mirande, Jean-Vianney; Wang, Minghui et al. (2018) Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol Psychiatry :
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211
Zhu, Carolyn W; Grossman, Hillel; Neugroschl, Judith et al. (2018) A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer's disease: A pilot study. Alzheimers Dement (N Y) 4:609-616
Boban, Mirta; Babi? Leko, Mirjana; Miški?, Terezija et al. (2018) Human neuroblastoma SH-SY5Y cells treated with okadaic acid express phosphorylated high molecular weight tau-immunoreactive protein species. J Neurosci Methods :

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