Image analysis of β-amyloid load in Alzheimer's disease and relation to dementia severity

Abstract

The protein β-amyloid is said to be central to the disease process of Alzheimer's disease (AD). Several groups have developed transgenic models that overexpress the amyloid precursor protein or β-amyloid and then develop AD-like neuropathology. Another report suggests that β-amyloid accumulation in old dogs correlates with cognitive impairment. However, many other researchers argue that β-amyloid deposition in senile plaques is a secondary event because plaque numbers in man do not correlate well with cognition. We set out to analyse this conumdrum in man. We selected 16 mild to severely demented AD cases on the basis of mini-mental state exam scores (MMSE; n=16). We also included 4 controls who represented the upper range of cognitive ability. We used a computer-based image analysis of cross-sectional area of the brain occupied by β-amyloid immunopositive deposition. We used this technique in preference to conventional methods of manual plaque counts and found a strong relation between β-amyloid load in entorhinal cortex and cognition measured on various scales (r=-0·93 versus the Blessed IMC). Our study suggests that the size of cortical area affected by β-amyloid deposition is an important factor in the clinical manifestation of dementia, and lends support to the possibility that β-amyloid is central to the aetiology of AD.