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Amyloid Precursor Protein in Platelets of Patients With Alzheimer Disease
Effect of Acetylcholinesterase Inhibitor Treatment
Barbara Borroni, MD;
Francesca Colciaghi, PhD;
Lucia Pastorino, PhD;
Carla Pettenati, MD;
Elisabetta Cottini, MD;
Luca Rozzini, MD;
Roberto Monastero, MD;
Gian Luigi Lenzi, MD;
Flaminio Cattabeni, PhD;
Monica Di Luca, PhD;
Alessandro Padovani, MD
Arch Neurol. 2001;58:442-446.
Background Amyloid precursor protein (APP) forms with apparent molecular weights
of 130, 110, and 106 kd are present in human platelets. It has been demonstrated
that Alzheimer disease (AD) is specifically associated with a decreased APP
forms ratio in platelets.
Objective To investigate whether acetylcholinesterase (AChE) inhibitor treatment
modifies the ratio of platelet APP forms in patients with AD.
Patients and Methods From a large sample of patients with probable AD, 30 with mild to moderate
AD were selected. Each patient underwent a clinical evaluation including the
Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline
and after 30 days. During this interval, 20 of 30 patients with AD were treated
with donepezil hydrochloride (5 mg/d), a piperidine phosphate–based
cholinesterase inhibitor. Platelets were subjected to Western blot analysis
using monoclonal antibody (22C11). The ratio between the immunoreactivity
of the higher-molecular-weight APP form (130 kd) and the lower forms (106
and 110 kd) was measured.
Results All patients taking donepezil completed the 30 days of treatment without
adverse effects. The platelet APP forms ratio at baseline did not differ between
the 2 AD groups (mean ± SD optical density ratio: untreated AD, 0.47
± 0.12; treated AD, 0.38 ± 0.18), whereas a significant difference
was found at follow-up (mean ± SD optical density ratio: untreated
AD, 0.45 ± 0.17; treated AD, 0.77 ± 0.29; P<.001). A significant improvement in MMSE scores in treated AD
patients was observed from baseline (16.9 ± 3.8) to 30 days (18.9 ±
4.42) (P<.009, 30 days vs baseline), but no significant
correlation was found in treated AD patients between MMSE score improvement
and APP forms/ratio increase (P = .09).
Conclusions Administration of AChE inhibitors increases the ratio of APP forms in
platelets of patients with AD, suggesting a potential effect of AChE inhibitors
on APP trafficking or processing in a peripheral cell.
From the Department of Neurology, University of Brescia, Brescia (Drs
Borroni, Cottini, Rozzini, Monastero, and Padovani); the Institute of Pharmacological
Sciences, University of Milan, Milan (Drs Colciaghi, Pastorino, Cattabeni,
and Di Luca); the Alzheimer Center, Passirana-Rho (Dr Pettenati); and the
Department of Neurology, "La Sapienza" University of Rome, Rome (Dr Lenzi),
Italy.
Corresponding author and reprints: Monica Di Luca, PhD, Institute
of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133
Milano, Italy (e-mail: Monica.Diluca{at}unimi.it).
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