. Flemish and Dutch mutations in amyloid beta precursor protein have different effects on amyloid beta secretion. Neurobiol Dis. 1998 Oct;5(4):281-6.


Mutations in the amyloid b precursor protein (APP) gene cosegregate with autosomal dominant Alzheimer's disease (AD). Brain pathology of AD is characterized by amyloid deposition in senile plaques and by neurofibrillary tangles. Amyloid deposits in AD brains consist of amyloid b (Ab), a 4-kDa proteolytic product of APP. In contrast, two other mutations in APP, the Flemish APP692 and Dutch APP693 mutations, are associated with autosomal dominant cerebral hemorrhages due to congophilic amyloid angiopathy (CAA) in the presence or absence of AD pathology, respectively. Both mutations are located within Ab near the constitutive cleavage site. While a common effect of AD-linked mutations is to elevate Ab42 extracellular concentrations, not much is known about the effect of APP692 and APP693. Here we provide evidence that APP692 and APP693 have a different effect on Ab secretion as determined by cDNA transfection experiments. While APP692 upregulates both Ab40 and Ab42 secretion, APP693 does not. These data corroborate with previous findings that increased Ab secretion and particularly of Ab42, is specific for AD pathology.


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  1. APP A692G (Flemish)