Raquel N. Taddei (United States of America)
Massachusetts General Hospital and Harvard Medical School
Neurology
Raquel N. Taddei is an MD and neurologist currently pursuing her PhD at Harvard University (USA) and University College London (UK). After obtaining her medical degree from the universities of Madrid and Munich she trained as a neurology resident in a number of university hospitals (Zurich, Geneva, Bern, and London). She obtained her Swiss and UK accredited neurologist diploma in 2020 and moved to Boston (USA) thereafter to pursue her academic career in Alzheimer’s disease (AD) dementia research. Her current PhD work focuses on glial derangements in earliest stages of tau pathology in human AD brains with the aim to disentangle the complexity of glial-tau interactions at the synapses in very early stages of the disease, and understand their association with cognitive impairment in AD. She has been supported by a number of scholarships and fellowships in 2021 and 2022 (Harvard University, USA), and has recently obtained her USA medical board license to pursue a sub-specialty training in clinical dementia, for which she has been appointed as a Clinical Fellow in Dementia (Growdon fellowship) at Massachusetts General Hospital led by Dr Gomez-Isla and starting in 2022.

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 Conference Calendar

WHITE MATTER (WM) ABNORMALITIES AS AN EARLY MARKER OF CORTICAL VULNERABILITY AND A DETERMINANT OF COGNITIVE DYSFUNCTION IN ALZHEIMER’S DISEASE (AD)

Session Name
0760 - DISEASE MECHANISMS, INFLAMMATION. MICROGLIA, ASTROCYTES, AMYLOIDS (ID 128)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 113
Lecture Time
04:00 PM - 04:15 PM
Presenter

Abstract

Aims

WM abnormalities constitute an early hallmark in AD pathogenesis, presenting many years prior to cortical neuronal loss and dementia. Yet, the underlying pathways and mechanisms linking subcortical and cortical pathogenic changes remain widely unexplored. We aimed to evaluate glial expression profiles in WM of individuals with differing cognitive statuses and address possible links with cortical markers of early cellular damage in AD.

Methods

We performed immunohistochemical analyses using artificial-intelligence based cell-quantifications of WM of demented and non-demented individuals with identical tau burden (Braak III/IV), and healthy controls. We evaluated brain regions temporally matched (temporal pole) and posterior (occipital cortex) to the tau deposition stage of these study subjects at postmortem, assessing diverging glial expression patterns.

Results

We found a differing WM expression profile with increased activated and reduced homeostatic glia, which was present in demented individuals in brain regions with and without overt tau deposition. In addition, we found an association between dysfunctional glia burden in subcortical-WM and presence of early cellular vulnerability markers in the cortex.

Conclusions

Our results suggest that WM dysfunction occurs early in AD and prior to overt cortical tau deposition. Moreover, dysfunctional glial profiles with an increase in activated and loss of homeostatic astroglia markedly differ between demented and non-demented individuals. Lastly, the burden of subcortical glial patterns shows association with cortical cellular vulnerability markers. Overall, these results suggest that WM could be an early site of vulnerability in AD and that its dysfunction could be key in subsequent cortical cellular loss, tau deposition and dementia in AD.

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