期刊
JOURNAL OF LIPID RESEARCH
卷 58, 期 5, 页码 824-836出版社
ELSEVIER
DOI: 10.1194/jlr.R075481
关键词
ATP binding cassete A1; apolipoproteins; brain lipids; high density lipoprotein
资金
- National Institutes of Health [NS090934, AG047644]
Alzheimer's disease (AD) is one of the fastest-growing causes of death and disability in persons 65 years of age or older, affecting more than 5 million Americans alone. Clinical manifestations of AD include progressive decline in memory, executive function, language, and other cognitive domains. Research efforts within the last three decades have identified APOE as the most significant genetic risk factor for late-onset AD, which accounts for >99% of cases. The apoE protein is hypothesized to affect AD pathogenesis through a variety of mechanisms, from its effects on the blood-brain barrier, the innate immune system, and synaptic function to the accumulation of amyloid-beta (A beta). Here, we discuss the role of apoE on the biophysical properties and metabolism of the A. peptide, the principal component of amyloid plaques and cerebral amyloid angiopathy (CAA). CAA is characterized by the deposition of amyloid proteins (including A beta) in the leptomeningeal medium and small arteries, which is found in most AD cases but sometimes occurs as an independent entity. Accumulation of these pathologies in the brain is one of the pathological hallmarks of AD.(Jlr) Beyond A beta, we will extend the discussion to the potential role of apoE on other amyloidogenic proteins found in AD, and also a number of diverse neurodegenerative diseases.
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