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. 2006 Apr 5;9(4):707–720. doi: 10.1111/j.1750-3639.1999.tb00552.x

Alpha‐synuclein in Lewy Body Disease and Alzheimer's Disease

Makoto Hashimoto 1, Eliezer Masliah 1,2,✉
PMCID: PMC8098211  PMID: 10517509

Abstract

Alzheimer's disease (AD) and Lewy body disease (LBD) are the most common causes of dementia in the elderly population. Previous studies have shown that cognitive alterations in these disorders are associated with synaptic loss. Injury and loss of synapses might be associated with altered function of synaptic proteins. Among them, recent studies have shown that abnormal aggregation and accumulation of synaptic proteins, such as α‐synuclein, might be associated with plaque formation in AD and Lewy body formation in LBD. Further reinforcing the hypothesis that α‐synuclein plays a major role in the pathogenesis of these disorders, recent work has shown that mutations that alter the conformation of this molecule are associated with familial forms of Parkinson's disease. The mechanisms by which altered function or aggregation of α‐synuclein might lead to neurodegeneration are not completely clear; however, new evidence points to a potential role for this molecule in synaptic damage and neurotoxicity via amyloid‐like fibril formation and mitochondrial dysfunction. In this manuscript we review the data linking α‐synuclein to the pathogenesis of AD and LBD.

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