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O3‐07‐08: Aβ42 immunization reduces both tau and Aβ deposits in Alzheimer's disease
Author(s) -
Boche Delphine,
Donald Jane,
Love Seth,
Neal James W.,
Holmes Clive,
Nicoll James
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.2019
Subject(s) - entorhinal cortex , hippocampus , neuroscience , subiculum , inferior parietal lobule , pathology , dementia , alzheimer's disease , hippocampal formation , dentate gyrus , neuropil , temporal cortex , medicine , neurodegeneration , disease , psychology , central nervous system , functional magnetic resonance imaging
Background: Alzheimer’s disease (AD) is the commonest cause of dementia and a major public health concern, particularly in ageing societies. AD pathology is characterised by abnormal aggregation in the brain of amyloid-b (Ab) peptide and hyperphosphorylated tau, although how these proteins interact in disease pathogenesis is unclear. Methods: We quantified Ab42 and phospho-tau in the brains of 10 AD patients who were actively immunised with Ab peptide (AN1792, Elan Pharmaceuticals) as a potentially disease-modifying therapeutic approach and compared the findings with those in 28 matched unimmunised AD cases. Immunostaining for Ab42 (21F12) and phospho-tau (AT8) was quantified in 6 different regions of cerebral grey matter which are affected by AD pathology (superior and middle temporal gyrus, medial frontal gyrus and inferior parietal lobule, entorhinal cortex, subiculum and CA1 hippocampus). Results: Not only was there a comparative reduction in Ab deposits in the cerebral cortex (cAD: 5.25% vs iAD: 1.42%; P 1⁄4 0.001) in the immunised patients but there was also a significant reduction in phospho-tau load in the same region (cAD: 1.08 % vs iAD: 0.72%, P 1⁄4 0.048). Similar changes were observed in the hippocampus. Assessment of the localisation within neurons of phosphotau indicated that the Ab immunotherapy-associated reduction was confined to neuronal processes i.e. neuropil threads (cAD: 1.08 % vs iAD: 0.72%, P 1⁄4 0.048) and dystrophic neurites (cAD: 53.5 vs iAD: 17 / 20 fields sampled; P 1⁄4 0.045). However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected (cAD: 259 vs IAD 311 / 20 fields samples; P 1⁄4 0.683). Conclusions: In showing that Ab immunisation can influence tau pathology, we demonstrate a link between these proteins and confirm the position of Ab as a target for modifying both Ab and tau accumulation in AD.