{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:03:42Z","timestamp":1791511422619,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,10,25]],"date-time":"2010-10-25T00:00:00Z","timestamp":1287964800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Amyloid\u2010\u03b2(A\u03b2) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 A\u03b2 and hyperphosphorylated tau (HP\u03c4). Adequate samples and the clinical follow\u2010up 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 A\u03b2 and\/or HP\u03c4 in the biopsy samples obtained during life predicted development of cognitive impairment, in particular, AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 433 frontal cortical samples, 42 (10%) displayed both A\u03b2 and HP\u03c4, 144 (33%) A\u03b2 only, and 247 (57%) neither A\u03b2 nor HP\u03c4. In a median follow\u2010up time of 4.4 years, 94 patients (22%) developed clinical AD. The presence of both A\u03b2 and HP\u03c4 was strongly associated (odds ratio [OR], 68.2; 95% confidence interval [CI], 22.1\u2013210) and A\u03b2 alone significantly associated (OR, 10.8; 95% CI, 4.9\u201323.8) with the clinical diagnosis of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This is the largest follow\u2010up study of patients assessed for the presence of A\u03b2 and HP\u03c4 in frontal cortical brain biopsy samples. 1) The presence of A\u03b2 and HP\u03c4 spoke strongly for the presence or later development of clinical AD; 2) A\u03b2 alone was suggestive of AD; and 3) the absence of A\u03b2 and HP\u03c4 spoke against a later clinical diagnosis of AD. 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