β‐amyloid burden is not associated with rates of brain atrophy

Abstract

Objective-To test the hypothesis that beta-amyloid (Aβ) burden is associated with rates of brain atrophy.Methods-Forty-five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease that had two volumetric head MRI scans were identified. Compact, as well as total (compact + diffuse) Aβ burden was measured using a computerized image analyzer with software program to detect the proportion of grey matter occupied by Aβ. Visual ratings of Aβ burden were also performed. The boundary-shift integral (BSI) was used to calculate change over time in whole brain and ventricular volume. All BSI results were annualized by adjusting for scan interval. Demographics, cognitive measures, clinical diagnoses, apolipoprotein E genotype, neurofibrillary tangle pathology, and vascular lesion burden were determined.Results-There was no correlation between compact or total Aβ burden, or visual Aβ ratings, and rates of brain loss or ventricular expansion in all subjects. However, significant correlations were observed between rates of brain loss and age, Braak stage, and change over time in cognitive measures. These features also correlated with rates of ventricular expansion. The rates of brain loss and ventricular expansion were greater in demented compared to non-demented subjects.Interpretation-These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Aβ in the grey matter.

Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease

“…Numerous studies have confirmed a quantitative link for the spread of neurofibrillary tangle pathology and the quantity of aggregated tau with both the extent of clinical dementia and functional molecular imaging deficits in Alzheimer's disease (AD) [5][6][7][8]. In light of the repeated failures of trials targeting the amyloid-␤ pathway in mild or moderate AD [9], there is increasing interest in the possibility that a tau aggregation inhibitor (TAI) could have therapeutic utility in AD [9][10][11].…”

P2‐143: Prediction of Alzheimer's disease pathophysiology based on cortical thickness patterns

“…Many experimental and clinical studies have demonstrated that Ab accumulation precedes tau-mediated neuronal injury and glucose hypometabolism [24,34,35]. At the same time, the extent of tau pathology but not Ab burden is known to correlate with the rate of atrophy in AD [4]. The lack of difference in amyloid uptake between the MT and D subtypes, but not in glucose hypometabolism or cortical atrophy patterns, may also stem from the fact that Ab builds up preclinically and reaches its maximal level by the time of clinical symptom development.…”

“…The accumulation of tau has been noted in the transentorhinal cortices with normal aging and such tau aggregation is known to accelerate the spread of Ab pathology in the AD brain [1][2][3]. Moreover, the accumulation of tau proteins correlates very closely with cognitive decline and brain atrophy including hippocampal atrophy [4,5]. Hence, defining AD based on the tau pathology in the brain would enable a better understanding of the clinical implications of tau accumulation in this disease.…”

Structural and mechanistic commonalities of amyloid-β and the prion protein

“…[12][13][14] However, these tangles are not solely associated with AD and are instead characteristic pathological features of an array of neurodegenerative diseases and other disorders such as subacute sclerosing panencephalitis. 4 Aβ neuritic plaques, despite being present in healthy and AD diseased brains as well as patients suffering from dementia with Lewy bodies (DLB), are not the major pathological traits of any other disease.…”