Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium

Abstract

β-Amyloid (Aβ) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as ι and α synuclein related lesions, also Aβ related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of Aβ, i.e. phase 1 = deposition of Aβ exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of Aβ phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of Aβ-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer’s disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the Aβ phase in AD is feasible even in large scale retrospective studies.

Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease

“…The predominantly parieto-occipital location of the WMH further supports the hypothesis that they relate to CAA. CAA, which is present to at least some degree in 70%e100% of AD brains at postmortem (Bergeron et al, 1987;Ellis et al, 1996), has a particular predilection for the occipital lobes (Alafuzoff et al, 2009;Thal et al, 2002), and a posterior distribution of WMH has been shown to predict pathologically confirmed CAA (Thanprasertsuk et al, 2014). Although only one of the APP subjects had a mutation within the Ab coding domain, their ARWMC score was considerably higher than the median for the APP group, consistent with pathological reports of severe CAA in cases with intradomain APP mutations.…”

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

“…Future studies should also aim to re-evaluate these observations to validate this approach and to develop a concise classification of ARTAG for diagnostic neuropathology. To reach this goal, paradigms will need to be designed for ARTAG along the lines used to standardize evaluation and diagnostic criteria for tau, amyloid and α-synuclein and other major pathologies [2–4, 10, 45]. Subsequently, it will be possible to evaluate inter-rater reliability of the proposed evaluation and eventually to merge clinical and pathologic data from multiple centers to determine practical significance of ARTAG.…”

Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort

“…For AD, the criteria of Braak were used modified for thin sections 17 and vascular amyloid ␤ deposits were assessed according to BrainNet Europe (BNE) instructions. 18 For FTLD, the Cairns classification was used. 19 For DLB, the Braak criteria were used 20 modified according to the BNE instructions.…”