Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Aβ42 immunisation in Alzheimer’s disease
Alzheimer’s disease (AD) pathology is characterised by aggregation in the brain of amyloid-β (Aβ) peptide and hyperphosphorylated tau (phospho-tau), although how these proteins interact in disease pathogenesis is unclear. Aβ immunisation results in removal of Aβ from the brain but cognitive decline continues to progress, possibly due to persistent phospho-tau. We quantified phospho-tau and Aβ42 in the brains of 10 AD patients (iAD) who were actively immunised with Aβ42 (AN1792, Elan Pharmaceuticals) compared with 28 unimmunised AD cases (cAD). The phospho-tau load was lower in the iAD than the cAD group in the cerebral cortex (cAD 1.08% vs. iAD 0.72%, P = 0.048), CA1 hippocampus (cAD 2.26% vs. iAD 1.05%; P = 0.001), subiculum (cAD 1.60% vs. iAD 0.31%; P = 0.001) and entorhinal cortex (cAD 1.10% vs. iAD 0.18%; P < 0.001). Assessment of the localisation within neurons of phospho-tau indicated that the Aβ immunotherapy-associated reduction was confined to neuronal processes, i.e. neuropil threads and dystrophic neurites. However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected. In showing that Aβ immunisation can influence phospho-tau pathology, we confirm the position of Aβ as a target for modifying tau accumulation in AD and demonstrate a link between these proteins. However, the continuing progression of cognitive decline in AD patients after Aβ immunisation may be explained by its lack of apparent effect on tangles.
KeywordsAlzheimer’s disease Tau Immunisation Amyloid
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