DIFFERENTIAL LEVEL OF PLATELET AMYLOID-BETA PRECURSOR PROTEIN ISOFORMS - AN EARLY MARKER FOR ALZHEIMER-DISEASE

Objective: To determine whether a differential level of platelet amylo id beta precursor protein (APP) isoforms is specifically related to Al zheimer disease (AD) and whether it shows a correlation with the progr ession of clinical symptoms. Design: After subjects were grouped accor ding to diagnosis and severity of dementia, APP isoform levels in plat elets were compared. Setting: University medical centers. Patients: Th irty-two patients who fulfilled diagnostic criteria for probable AD, 2 5 age-matched control subjects, and 16 patients with non-AD dementia. Main Outcome Measure: The levels of APP isoforms were evaluated by mea ns of Western blot analysis and immunostaining of whole platelets. Mes senger RNAs for APP transcripts were also evaluated by means of revers e transcriptase polymerase chain reaction. Results: The ratio between the intensity of the 130-kd and 106- to 110-kd APP isoforms was signif icantly lower in the AD group (0.31 +/- 0.15, mean +/- SD) compared wi th both controls (0.84 +/- 0.2) and non-AD subjects (0.97 +/- 0.4). Th e ratio of platelet APP isoforms in patients with AD grouped by Clinic al Diagnostic Rating score significantly correlated with the severity of the disease (Pearson correlation coefficient, followed by Bonferron i correction, P = .01). Reverse transcriptase polymerase chain reactio n experiments showed that APP transcripts in all experimental groups w ere equally expressed. Conclusions: The pattern of platelet APP isofor ms is specifically altered in patients with AD. In addition, the alter ation of platelet APP isoforms shows a positive correlation with the p rogression of clinical symptoms, supporting the possibility to conside r this peripheral parameter as a marker of progression of the disease. These alterations are not related to abnormalities of APP isoforms me ssenger RNAs in platelets.