Amyloid and tau proteins in cortical brain biopsy and Alzheimer's disease

• Published in: Annals of neurology Vol. 68; no. 4; pp. 446 - 453
• Main Authors: Leinonen, Ville, Koivisto, Anne M., Savolainen, Sakari, Rummukainen, Jaana, Tamminen, Juuso N., Tillgren, Tomi, Vainikka, Sannakaisa, Pyykkö, Okko T., Mölsä, Juhani, Fraunberg, Mikael, Pirttilä, Tuula, Jääskeläinen, Juha E., Soininen, Hilkka, Rinne, Jaakko, Alafuzoff, Irina
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2010; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Biological and medical sciences; Biopsy - methods; Cerebral Cortex - metabolism; Cognition Disorders - etiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dermatologi och venerologi, klinisk genetik, invärtesmedicin; Dermatology and venerology,clinical genetics, internal medicine; Female; Finland; Humans; Internal medicine; Invärtesmedicin; Logistic Models; Longitudinal Studies; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Neurologi; Neurology; Psychiatric Status Rating Scales; Retrospective Studies; Sensitivity and Specificity; tau Proteins - metabolism; Finland; Nervous system diseases; Tau protein; Biopsy; Alzheimer disease; Central nervous system disease; Degenerative disease; Amyloid; Cerebral disorder
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.22100

Objective Amyloid‐β(Aβ) aggregates are presumed to be found in the brain at an early stage of Alzheimer's disease (AD) but have seldom been assessed by brain biopsy during life in often elderly patients. Methods Between 1991 and 2006 we evaluated 468 patients with suspected normal pressure hydrocephalus with intraventricular pressure monitoring and a right frontal cortical biopsy sample immunostained for Aβ and hyperphosphorylated tau (HPτ). Adequate samples and the clinical follow‐up data until death or the end of 2008, available in 433 cases, were reviewed for the clinical signs of dementia, including AD. Logistic regression analysis was used to analyze whether Aβ and/or HPτ in the biopsy samples obtained during life predicted development of cognitive impairment, in particular, AD. Results Of the 433 frontal cortical samples, 42 (10%) displayed both Aβ and HPτ, 144 (33%) Aβ only, and 247 (57%) neither Aβ nor HPτ. In a median follow‐up time of 4.4 years, 94 patients (22%) developed clinical AD. The presence of both Aβ and HPτ was strongly associated (odds ratio [OR], 68.2; 95% confidence interval [CI], 22.1–210) and Aβ alone significantly associated (OR, 10.8; 95% CI, 4.9–23.8) with the clinical diagnosis of AD. Interpretation This is the largest follow‐up study of patients assessed for the presence of Aβ and HPτ in frontal cortical brain biopsy samples. 1) The presence of Aβ and HPτ spoke strongly for the presence or later development of clinical AD; 2) Aβ alone was suggestive of AD; and 3) the absence of Aβ and HPτ spoke against a later clinical diagnosis of AD. Ann Neurol 2010;68:446–453