Abstract：
:A key neuropathological hallmark of Alzheimer's disease (AD) is the loss of neocortical and hippocampal synapses, which is closely correlated with the degree of memory impairment. Mutations in the genes encoding the amyloid precursorprotein (APP) and presenilins are responsible from some cases of early-onset autosomal-dominant AD. This article reviews the current understanding of how alterations in the cellular functions of APP and presenilins may result in the dysfunction and degeneration of synapses in AD. APP mutations result in increased production/aggregation of amyloid beta-peptide (Abeta), which induces oxidative stress, resulting in the impairment of synaptic membrane ion, glutamate, and glucose transporters. APP mutations may also compromise the production and/or function of secreted forms of APP that are believed to play important roles in learning and memory processes. Presenilin (PS1) mutations result in a major defect in endoplasmic reticulum (ER) calcium regulation, which may perturb synaptic function in ways that lead to impaired synaptic plasticity and neuronal degeneration. Studies in transgenic mice that express APP and PS1 mutations have provided evidence that the mutations result in altered cellular calcium homeostasis and synaptic plasticity, and impaired learning and memory. This article provides a brief review of the pathophysiological interactions of APP and presenilins with synaptic proteins, and discusses how AD-linked mutations in APP and PS1 may disrupt synaptic processes that contribute to memory formation.
journal_name
Neuromolecular Medjournal_title
Neuromolecular medicineauthors
Chan SL,Furukawa K,Mattson MPdoi
10.1385/NMM:2:2:167keywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
167-96issue
2eissn
1535-1084issn
1559-1174pii
NMM:2:2:167journal_volume
2pub_type
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