Abstract Details

Title Reduced Alzheimer’s Disease Pathology in the Association Cortex after Traumatic Disconnection of the Mesial Temporal Lobe in Human Post-mortem Brain Tissue

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 13-006

Objective

To evaluate the effect of mesial temporal lobe (MTL) disconnection on the distribution of Alzheimer’s disease (AD) pathology using rare post-mortem tissue from World War II veterans who survived 50 years after unilateral penetrating brain injuries.

Background

AD pathology is defined by amyloid-beta (aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (p-tau). NFTs appear to spread from the MTL to the association cortices (AC), matching clinical progression of AD. In vitro and animal studies support the tau propagation hypothesis, suggesting that p-tau moves through the brain along neurons and across synapses. This pathway represents an important target in the search for disease-modifying AD treatments, but there is currently limited evidence in humans.

Design/Methods

The extent of AD pathology was assessed in the MTL and AC of lesional and non-lesional hemispheres from 15 veterans. Systematic quantitative neuropathological methods were applied to measure aβ plaque area coverage (%Aβ) and the proportion of neurons affected by NFTs (%NFT). Traumatic disconnection of the MTL and AC was defined using 3D digital lesion reconstructions generated from post-mortem reports and anatomical photographs. Clustered statistics were used to perform within-case comparisons.

Results

The overall extent of AD pathology was equal between hemispheres (%Aβ: lesional=1.23%, non-lesional=1.72%, χ²=1.358, p=0.244; %NFT: lesional=7.89%, non-lesional=9.25%, χ²=0.476, p=0.490). %Aβ was equal in the MTL and AC (MTL=1.60%, AC=1.11%, χ²=2.009, p=0.156) while %NFT was lower in the AC than MTL (MTL=10.5%, AC=3.46%, χ²=11.360, p<0.001). %NFT was more markedly reduced in the AC of the lesional hemisphere (MTL=10.19%, AC=1.70%, p<0.001) than the non-lesional hemisphere (MTL=10.79%, AC: 5.09%, p=0.039). Traumatic disconnection of the MTL reduced %NFT in the AC compared with the contralateral hemisphere, adjusting for %NFT in the ipsilateral MTL (disconnected=0.86%, connected=3.16%, p=0.015).

Conclusions

Traumatic disconnection of the MTL reduced AD-related p-tau pathology in the AC. This provides novel evidence supporting the tau propagation hypothesis in humans.

Authors/Disclosures
Jonathan E. Attwood, MBBS (Nuffield Department of Clinical Neurosciences) PRESENTER	The institution of Dr. Attwood has received research support from the Medical Research Council (UK). The institution of Dr. Attwood has received research support from the British Neuropathological Society. The institution of Dr. Attwood has received research support from the American Academy of Neurology.
Jonathan Pansieri, PhD (University of Oxford)	The institution of Dr. Pansieri has received research support from UK-MS society. The institution of Dr. Pansieri has received research support from Department of Defense US. Dr. Pansieri has received personal compensation in the range of $0-$499 for serving as a member of the Grant review Panel with French National Agency. Dr. Pansieri has received personal compensation in the range of $500-$4,999 for serving as a recipee of Travel Grant with Brain.
Marco Pisa, MD (Nuffield Department of Clinical Neurosciences, University of Oxford)	Dr. Pisa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Margaret Esiri	Margaret Esiri has stock in Cytox Group.
Edward de Haan, PhD	Prof. de Haan has nothing to disclose.
Gabriele C. De Luca, MD, DPhil, FRCPath, FAAN (University of Oxford)	Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurology Academy. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wellcome Trust. The institution of Dr. De Luca has received research support from National Health and Medical Research (Australia). The institution of Dr. De Luca has received research support from UK MS Society. The institution of Dr. De Luca has received research support from Oxford-Quinnipiac Partnership. The institution of Dr. De Luca has received research support from US Department of Defense. The institution of Dr. De Luca has received research support from National Health and Medical Research (Australia). The institution of Dr. De Luca has received research support from Rosetrees Trust. The institution of Dr. De Luca has received research support from Strategic Innovation Fund, Oxford University. The institution of Dr. De Luca has received research support from Agence National de la Recherche. Dr. De Luca has a non-compensated relationship as a Editorial board member with MS Journal that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Steering Group member with MS Academy that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Board of Directors with SEQUINS that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Editorial board member with Continuum (AAN) that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Editorial board member with Frontiers in Neurology that is relevant to AAN interests or activities.