The role of the amyloid protein precursor (APP) in Alzheimer's disease: does the normal function of APP explain the topography of neurodegeneration?

Abstract:

:Alzheimer's disease (AD) is the most common form of dementia in the aged population. Early-onset familial AD (FAD) involves mutations in a gene on chromosome 21 encoding the amyloid protein precursor or on chromosomes 14 or 1 encoding genes known as presenilins. All mutations examined have been found to increase the production of amyloidogenic forms of the amyloid protein (A beta), a 4 kDa peptide derived from APP. Despite the remarkable progress in elucidating the biochemical mechanisms responsible for AD, little is known about the normal function of APP. A model of how APP and A beta are involved in pathogenesis is presented. This model may explain why certain neuronal populations are selectively vulnerable in AD. It is suggested that those neurons which more readily undergo neuritic sprouting and synaptic remodelling are more vulnerable to A beta neurotoxicity.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Small DH

doi

10.1023/a:1022471729291

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

795-806

issue

5

eissn

0364-3190

issn

1573-6903

journal_volume

23

pub_type

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