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Position 717 in the amyloid precursor protein (APP) is a hotspot for mutations associated with autosomal dominant AD (ADAD) and the valine to isoleucine amino acid substitution (V717I) at this position was among the first ADAD mutations identified, spearheading the formulation of the amyloid cascade hypothesis of AD pathogenesis. While this mutation is well described in multiple kindreds and has served as the basis for the generation of widely used animal models of disease, neuropathologic data on patients carrying this mutation are scarce. Here we present the detailed clinical and neuropathologic characterization of an APP V717I carrier, which reveals important novel insights into the phenotypic variability of ADAD cases. While age at onset, clinical presentation and widespread parenchymal beta-amyloid (A\u03b2) deposition are in line with previous reports, our case also shows widespread and severe cerebral amyloid angiopathy (CAA). This patient also presented with TDP-43 pathology in the hippocampus and amygdala, consistent with limbic predominant age-related TDP-43 proteinopathy (LATE). The APOE \u03b52\/\u03b53 genotype may have been a major driver of the prominent vascular pathology seen in our case. These findings highlight the importance of neuropathologic examinations of genetically determined AD cases and demonstrate striking phenotypic variability in ADAD cases.<\/jats:p>","DOI":"10.1186\/s40478-020-0891-3","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T14:02:50Z","timestamp":1584021770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier \u2013 phenotypic variability in autosomal dominant Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"8","author":[{"given":"Grace M.","family":"Lloyd","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge A.","family":"Trejo-Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxing","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen N.","family":"McFarland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Lincoln","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nil\u00fcfer","family":"Ertekin-Taner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit I.","family":"Giasson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony T.","family":"Yachnis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-2149","authenticated-orcid":false,"given":"Stefan","family":"Prokop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"891_CR1","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1023\/A:1021910729963","volume":"22","author":"H Akiyama","year":"1997","unstructured":"Akiyama H, Mori H, Sahara N, Kondo H, Ikeda K, Nishimura T, Oda T, McGeer PL (1997) Variable deposition of amyloid \u03b2-protein (A\u03b2) with the carboxy- terminus that ends at residue valine40 (A\u03b240) in the cerebral cortex of patients with Alzheimer\u2019s disease: a double-labeling immunohistochemical study with antibodies. 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