Studying more than 6000 amyloid plaques immunostained for total Aβ (Aβt), Aβ40 or Aβ42, we show here that Aβ40 FD could efficiently differentiate between (i) AD patients and aged-control individuals (P<0.001); (ii) sporadic and familial AD due to presenilin-1 or APP (A692G) mutations (P<0.001); and (iii) three transgenic mouse models of different genotypes (P<0.001).
We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores.
While patients with the Dutch APP mutation (E693Q) have predominantly hemorrhagic strokes, Flemish APP (A692G) patients develop both strokes and Alzheimer's disease (AD).
This was unusually severe CAA reminiscent of the Flemish amyloid precursor protein (A692G) mutation we reported previously, which causes Alzheimer's disease and/or cerebral haemorrhages.
The contribution of mutations in the amyloid precursor protein (APP) gene known as Flemish (APP/A692G) and Dutch (APP/E693Q) to the pathogenesis of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type, respectively, was studied in transgenic mice that overexpress the mutant APP in brain.