The origin of the various components of senile plaques in Alzheimer's disease (AD) continues to be a focus of intense research scrutiny. Lysosomal enzyme activity within the plaques is of particular interest because of its possible relevance to a presumed abnormal processing of precursor molecules that may lead to the formation of plaque amyloid. Histochemical evidence of acid phosphatase (ACP), a lysosomal hydrolase, activity in senile plaques has been documented long before many of the current biochemical data regarding plaque pathogenesis became available. Recent evidence suggests the presence of neuronal membrane abnormalities that may allow 'leakage' of some intracellular molecules, including enzymes, into the perineuronal environment and from there, possibly, to the cerebrospinal fluid (CSF). In the course of investigating this hypothesis, we decided to readdress the issue of ACP activity in AD by assaying the enzyme both in brain tissue sections as well as in CSF samples from neuropathologically confirmed cases of AD and from normal control subjects. Brain frozen sections from five cases with AD and five control subjects were histochemically stained for ACP using the α- naphthyl-phosphate hydrolysis method. Frozen CSF samples from 15 cases with AD and 19 control subjects were assayed for ACP activity using the thymolphthalein monophosphate hydrolysis method. In all cases studied, CSFs were cytologically unremarkable. Neurons in normal and AD brains were strongly positive for ACP. In AD, numerous senile plaques showed strong ACP activity with both granular and diffuse patterns. The CSFs from six of 15 AD cases (40%) showed ACP activity with values ranging from 0.04 to 0.4 U/L. No ACP activity was detected in any of the 19 control CSFs analyzed. The exact source of ACP in senile plaques and CSF of patients with AD cannot be established based on these data alone but the ACP may have originated from neurons with oxidative stress or oxygen free radical-mediated membrane damage. The data encourage further investigation of this hypothesis.
|Original language||English (US)|
|Number of pages||4|
|Journal||Archives of Pathology and Laboratory Medicine|
|State||Published - Jan 1 1993|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Medical Laboratory Technology