Differential level of platelet amyloid β precursor protein isoforms: An early marker for Alzheimer disease

Objective: To determine whether a differential level of platelet amyloid β precursor protein (APP) isoforms is specifically related to Alzheimer disease (AD) and whether it shows a correlation with the progression of clinical symptoms. Design: After subjects were grouped according to diagnosis and severity of dementia, APP isoform levels in platelets were compared. Setting: University medical centers. Patients: Thirty-two patients who fulfilled diagnostic criteria for probable AD, 25 age-matched control subjects, and 16 patients with non-AD dementia. Main Outcome Measure: The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. Messenger RNAs for APP transcripts were also evaluated by means of reverse transcriptase polymerase chain reaction. Results: The ratio between the intensity of the 130-kd and 106- to 110-kd APP isoforms was significantly lower in the AD group (0.31 ± 0.15, mean ± SD) compared with both controls (0.84 ± 0.2) and non-AD subjects (0.97 ± 0.4). The ratio of platelet APP isoforms in patients with AD grouped by Clinical Diagnostic Rating score significantly correlated with the severity of the disease (Pearson correlation coefficient, followed by Bonferroni correction, P = .01). Reverse transcriptase polymerase chain reaction experiments showed that APP transcripts in all experimental groups were equally expressed. Conclusions: The pattern of platelet APP isoforms is specifically altered in patients with AD. In addition, the alteration of platelet APP isoforms shows a positive correlation with the progression of clinical symptoms, supporting the possibility to consider this peripheral parameter as a marker of progression of the disease. These alterations are not related to abnormalities of APP isoforms messenger RNAs in platelets.