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Neurology 2001;57:2243-2248
© 2001 American Academy of Neurology


Articles

Amyloid precursor protein in platelets

A peripheral marker for the diagnosis of sporadic AD

A. Padovani, MD PhD;, L. Pastorino, PhD, B. Borroni, MD, F. Colciaghi, PhD, L. Rozzini, MD, R. Monastero, MD, J. Perez, MD PhD;, C. Pettenati, MD, M. Mussi, MD, G. Parrinello, PhD, E. Cottini, MD, G. L. Lenzi, MD, M. Trabucchi, MD, F. Cattabeni, PhD and M. Di Luca, PhD

From Dipt. Scienze Mediche e Chirurgiche (Drs. Padovani, Borroni, Rozzini, Cottini, and Monastero), Unità di Neurologia, Università degli Studi di Brescia; Istituto di Scienze Farmacologiche (Drs. Cattabeni, Colciaghi, Di Luca, and Pastorino), Università di Milano; Dipt. Scienze Neuropsicologiche (Dr. Perez), H. San Raffaele di Milano; Centro Alzheimer di Passirana-Rho (Milano) presso Azienda G. Salvini (Drs. Mussi and Pettenati); Dipt. di Scienze Neurologiche (Dr. Lenzi), Università di Roma La Sapienza; Gruppo di Ricerca Geriatria (GRG), Brescia (Dr. Trabucchi); Istituto di Biostatistica (Dr. Parrinello), Università degli Studi di Brescia, Italy.

Address correspondence and reprints requests to Dr. Alessandro Padovani, Dipartimento Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia Piazza Ospedale 1, 25125, Brescia, Italia; email: padovani{at}bshosp.osp.unibs.it

Background: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD.

Objective: To evaluate the sensitivity and the specificity of platelet APP forms’ ratio (APPr) as a marker for AD.

Methods: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands.

Results: Mean APPr levels were decreased in AD patients (mean OD ± SD = 0.35 ± 0.18) compared with the CON group (mean OD ± SD = 0.92 ± 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05).

Conclusion: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.




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F. Colciaghi, E. Marcello, B. Borroni, M. Zimmermann, C. Caltagirone, F. Cattabeni, A. Padovani, and M. Di Luca
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B. Borroni, F. Colciaghi, C. Caltagirone, L. Rozzini, L. Broglio, F. Cattabeni, M. Di Luca, and A. Padovani
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