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Differential Level of Platelet Amyloid  Precursor Protein Isoforms
An Early Marker for Alzheimer Disease
Monica Di Luca, PhD;
Lucia Pastorino, PhD;
Angelo Bianchetti, MD;
Jorge Perez, MD, PhD;
Luigi A. Vignolo, MD;
Gian Luigi Lenzi, MD;
Marco Trabucchi, MD;
Flaminio Cattabeni, PhD;
Alessandro Padovani, MD, PhD
Arch Neurol. 1998;55:1195-1200.
Objective To determine whether a differential level of platelet amyloid  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.
From the Institute of Pharmacological Sciences, University of Milan, Milan, Italy (Drs Di Luca, Pastorino, Perez, and Cattabeni); Alzheimer Disease Unit, Sacro Cuore Fatebenefratelli Hospital, IRCCS, San Giovanni di Dio, Brescia, Italy (Drs Bianchetti); Institute of Neurology, University of Brescia (Drs Vignolo and Padovani); Department of Neurological Sciences, University of Rome, Rome, Italy (Dr Lenzi); and Geriatric Research Group, Brescia (Dr Trabucchi).
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