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

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.