Alzheimer’s disease (AD) is a multifactorial, neurodegenerative disorder that accounts for nearly 70% of all dementia cases. AD is characterized by impaired memory, cognitive decline and pathological hallmarks including brain atrophy, neuronal death, and the accumulation of amyloid-β plaques and tau protein neurofibrillary tangles. AD currently has no cure, and no single genetic cause has been identified. It is typically categorized as either familial (early-onset) or sporadic (late-onset), with an age threshold of 65 years. Both forms are influenced by genetic variability affecting biochemical pathways prior to clinical manifestation, and in some cases, patients may carry gene duplications or pathogenic mutations. Apolipoprotein E (APOE) variants are associated with AD risk. The APOEε3 haplotype has a neutral risk for AD; however, one variant of APOEε3, known as the Christchurch variant, has been seen to prolong AD onset in some people. A patient who carried the autosomal dominant AD mutant of PSEN1 and was homozygous for the Christchurch variant presented with an abundance of Aβ and limited tau pathology in the brain alongside atypical amyloid distribution. AD onset was delayed for three years beyond expected onset. It is hypothesized that the Christchurch variant influences amyloid distribution, age of onset, and clinical presentation of AD. Here, we identified and reconstructed the amyloids present in the occipital and frontal cortices of an affected brain to verify the location of the amyloids as previously presented by immunohistochemical staining. 3D reconstructions of tau PHF and amyloid-β filaments were determined using RELION and refined with ServalCat.
Hinton et al. (Sun,) studied this question.