We have analysed several markers for small synaptic vesicles (
synaptin-
synaptophysin, p65 and SV2) and large dense-core vesicles (
chromogranin A,
secretogranin II/
chromogranin C) in the brains of patients with
Alzheimer's disease, and normal controls by immunoblotting and immunohistochemistry. In comparison to age-matched controls the levels of all three synaptic vesicle markers were decreased in temporal cortex of Alzheimer patients. On the other hand, the levels of
chromogranin A were increased, and those of
secretogranin II lowered. This resulted in a significant increase of the ratios of
chromogranin A to
synaptophysin, p65 or SV2 and of that for
chromogranin A to
secretogranin II. These increases were significantly correlated to clinical severity of
dementia and extent of neuropathological changes. By immunohistochemistry a high percentage of
senile plaques was found to contain
chromogranin A-reactive dystrophic neurites, whereas
synaptophysin reactivity within plaques was rare. These results indicate that the number of synaptic vesicles is lowered in
Alzheimer's disease, and that one component of large dense-core vesicles, i.e.
chromogranin A, is elevated. We, thus, suggest that in Alzheimer's brain distinct changes occur for both types of synaptic organelles.