Platelet APP isoform ratios correlate with declining cognition in AD.
BACKGROUND
Platelets and neurons both contain large quantities of two carboxyl-truncated 120 to 130 and 110 kDa Alzheimer amyloid precursor proteins (APPs). Platelets taken from patients with AD have been reported to contain a reduced ratio of these APPs.


OBJECTIVE
To further study the AD specificity of reduced platelet APP ratios and to determine whether, after 3 years, cognitive losses in AD are accompanied by similarly reduced platelet APP ratios.


METHODS
To test the AD specificity of reduced platelet APP ratios, we quantitated these APPs in eight patients with PD and six patients with hemorrhagic stroke (HS). To determine whether further cognitive losses correlate with platelet APP ratio reductions in patients with AD, the authors re-examined platelet APPs and Mini-Mental State Examination (MMSE) scores of 10 patients with AD and 11 controls, who were tested 3 years ago. APP ratios were determined by the average of six assays using Western blotting with m22C11 monoclonal antibody, enhanced chemoluminescence, and digital scanning of autoradiographs.


RESULTS
APP ratios were normal in the patients with PD and HS, further supporting the AD specificity of this assay. After 3 years, the MMSE scores and APP ratios of our control subjects changed by <4%. However, the average MMSE scores of our patients with AD declined from 16.4 to 8.3, and their average 120 to 130/110 kDa APP ratios declined from 5.8 to 3.6. The difference between AD and control APP ratios, with no overlap, is significant and the correlation between the 3-year decline in AD MMSE scores and reduced APP ratios (r = 0.69) was significant.


CONCLUSIONS
Although the number of subjects analyzed was limited, reduced platelet APP ratios appear to be a specific biological marker of AD and a biological index of the severity of cognitive loss in AD.
Baskin
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Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9036, USA. Fbaski@mednet.swmed.edu
Rosenberg
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Iyer
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Hynan
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Cullum
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D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012016:Reference Values
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers