Divergent Cognitive Status with the Same Braak Stage of Neurofibrillary Pathology: Does the Pattern of Amyloid-β Deposits Make the Difference?

Abstract

The neuropathological hallmark of Alzheimer's disease (AD) is the co-occurrence of extracellular amyloid-β (Aβ) deposition and intraneuronal neurofibrillary changes composed of abnormal tau. Over the last decades, the concept emerged that neurofibrillary changes progress in a hierarchical manner from mesial temporal structures through the associative neocortex to primary sensory and motor fields, paralleling cognitive deterioration closer than Aβ. The observation that two patients (one cognitively normal, one with dementia) exhibited neurofibrillary changes closely overlapping as regards their entity and topographic distribution but differed for characteristics of Aβ deposition suggests that the latter may directly contribute in determining cognitive impairment in AD.

Stereological approaches to dementia research using human brain tissue

“…An alternative approach in the elucidation of the temporal sequence of morphometric changes under neurodegenerative conditions is to use cases with varying degrees of neuropathological burden. Such an approach relies on the current staging schemes to accurately reflect the cognitive status of the individual and there is good evidence that they are good general indicators of cognition (Maderna et al, 2015, Price et al, 2009, with notable exceptions in the relationship between pathology and clinical phenotype (Gertz et al, 1998). Such studies, however, are particularly useful in identifying relationships between the spread of pathological lesions to different regions and the corresponding effects on cellular populations.…”

PET Imaging of Epigenetic Influences on Alzheimer’s Disease

“…A β deposits and tau tangles are required elements for the histopathological confirmation of an AD diagnosis [ 10 ]. Indeed, autopsy assessment indicating the presence of A β deposits and tau tangles is reported to be sufficient to account for the cognitive impairment in AD; however, the relative importance of the A β deposits versus the tau tangles is arguable [ 11 , 12 ]. Other factors including, but not limited to, white matter lesions and related cerebral blood flow decrements [ 13 ], as well as vascular lesions involving blood-brain barrier breakdown [ 14 ], may contribute to the cognitive deficits observed in AD.…”