title: Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology.
abstract: The cytoskeletal pathology of a patient with familial Alzheimer's disease (AD) associated with the probably causal amyloid precursor protein (APP) codon 717 Val----Ile mutation is described. In addition to moderately extensive beta A4 protein deposition within the substance of the brain and in blood vessel walls (congophilic angiopathy), there was abundant cytoskeletal pathology in the form of neurofibrillary tangles, plaque neurites and neuropil threads. Interestingly, plentiful cortical and subcortical Lewy bodies were also seen. In order to compare the cytoskeletal pathology in this case with that seen in sporadic cases of AD we (1) studied the immunohistochemical profile of the amyloid and cytoskeletal pathology with antibodies to beta A4 protein, tau, phosphorylated neurofilament epitopes and ubiquitin and (2) performed a biochemical fractionation and Western blot analysis for the abnormally phosphorylated form of tau (A68) characteristically seen in AD. No substantial difference between the familial case and sporadic cases could be found. We conclude that it is now reasonable to hypothesise that an abnormality in APP metabolism is responsible not only for the deposition of beta A4 protein, but also for the range of cytoskeletal pathology, typical of AD.
authors.affiliation: Department of Neuropathology, Institute of Psychiatry, London, UK.
authors.forename: P L
authors.initials: PL
authors.lastname: Lantos
authors.forename: P J
authors.initials: PJ
authors.lastname: Luthert
authors.forename: D
authors.initials: D
authors.lastname: Hanger
authors.forename: B H
authors.initials: BH
authors.lastname: Anderton
authors.forename: M
authors.initials: M
authors.lastname: Mullan
authors.forename: M
authors.initials: M
authors.lastname: Rossor
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D015153:Blotting, Western; D001923:Brain Chemistry; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D009154:Mutation; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000096:biosynthesis
chemical_list: D016564:Amyloid beta-Protein Precursor; D016900:Neurofilament Proteins; D016875:tau Proteins