Serge Gauthier

β-Amyloid precursor protein is detectable on monocytes and is increased in Alzheimer’s disease

Using the anti-beta-amyloid precursor protein (βAPP) monoclonal antibodies 4G8, 6E10 and 22C11 and flow cytometry, we report that human circulating peripheral blood monocytes display surface immunoreactivity for βAPP. In contrast, circulating lymphocytes do not possess cell surface βAPP immunoreactivity, despite similar levels of βAPP expression. Immunoblotting analysis showed that monocytes, but not lymphocytes, possess an 82kDa C-terminal βAPP fragment consistent with a processed transmembrane species. Monocyte surface βAPP was upregulated ∼threefold by activation with lipopolysaccharide and interferon-γ; activation did not produce detectable βAPP on the cell surface of lymphocytes. Surface βAPP immunoreactivity was reduced in a normal aged population compared to normal young controls (Young = 81.07 ± 13.67 mean fluorescence units, Aged = 36.74 ± 3.81, p < 0.01), but was significantly increased in AD subjects compared to age-matched healthy controls (AD = 60.31 ± 7.42, p < 0.05). Our data suggest that a proportion of peripheral Aβ may be derived from monocyte/macrophages, and that defects in brain cell processing of βAPP in AD may be shared by this readily accessible peripheral cell.

CSF acetylcholinesterase in dementia and in sequential samples of lumbar CSF

Acetylcholinesterase (AchE) activity (nmol/ml/min) was measured in lumbar CSF from 11 patients with dementia of the Alzheimer type (DAT), 8 patients with Korsakoff psychosis and 33 patients with low back pain who were undergoing myelography (controls). There was no significant difference in enzyme activity between the three groups. There was no significant correlation between age and AchE activity. AchE was also measured in 20 two-ml samples of CSF collected sequentially by lumbar puncture in two neurosurgical patients who had been recumbent for at least 8 hours. Variations in AchE between samples were small. In neither patient was there an increase in AchE activity with progressive sampling. These data indicate that (1) AchE is unchanged in Korsakoff psychosis (2) decreases in brain AchE which are found in DAT are not readily reflected in lumbar CSF (3) AchE in lumbar CSF has a diffuse origin including spinal cord (4) CSF AchE activity is unlikely to be a useful clinical marker for DAT.

Antemortem laboratory diagnosis of Alzheimer's disease.

The accuracy of diagnosis for AD by conventional clinical and laboratory means is in the order of 80%. Neurophysiological techniques (EEG, evoked potentials) show abnormalities in AD that could prove to be useful for diagnosis after pharmacological challenges. CSF analysis show a reduction of the concentration of various neuropeptides, reduction shared by other types of dementias. Among the existing imaging techniques PET using 18F-fluorodeoxyglucose is the most diagnostic in AD because of the early and often asymmetrical decrease in parietotemporal metabolic activity. Cortical biopsy with histological and biochemical analysis can provide an accurate in vivo diagnosis of AD.

Practical guidelines for the antemortem diagnosis of senile dementia of the alzheimer type

SDAT is the most common type of dementia in the elderly but is difficult to diagnose antemortem. The clinical assessment gives a 80% accuracy of diagnosis. 18F-DG is currently the best imaging technique for the diagnosis of SDAT in vivo. A cortical biopsy with histology and assay of CAT is required to give a diagnosis of definite SDAT.