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Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. In post\u2010mortem studies, total SVD pathology in cortical areas and basal ganglia was similar in <jats:italic>PSEN1<\/jats:italic> FAD and CADASIL subjects, except for the feature of arteriosclerosis which was higher in CADASIL subjects than in <jats:italic>PSEN1<\/jats:italic> FAD subjects. Further only a few SAD subjects showed a similar degree of SVD pathology as observed in CADASIL. Furthermore, we found significantly enlarged perivascular spaces in vessels devoid of cerebral amyloid angiopathy in FAD compared with SAD and CADASIL subjects. As expected, there was greater fibrinogen\u2010positive perivascular reactivity in CADASIL but similar reactivity in <jats:italic>PSEN1<\/jats:italic> FAD and SAD groups. Fibrinogen immunoreactivity correlated with onset age in the <jats:italic>PSEN1<\/jats:italic> FAD cases, suggesting increased vascular permeability may contribute to cognitive decline. Additionally, we found reduced perivascular expression of PDGFR\u03b2 AQP4 in microvessels with enlarged PVS in <jats:italic>PSEN1<\/jats:italic> FAD cases. We demonstrate that there is A\u03b2\u2010independent SVD pathology in <jats:italic>PSEN1<\/jats:italic> FAD, that was marginally lower than that in CADASIL subjects although not evident by MRI. These observations suggest presence of covert SVD even in <jats:italic>PSEN1<\/jats:italic>, contributing to disease progression. As is the case in SAD, these consequences may be preventable by early recognition and actively controlling vascular disease risk, even in familial forms of dementia.<\/jats:p>","DOI":"10.1111\/bpa.13097","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T14:27:37Z","timestamp":1655130457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease"],"prefix":"10.1111","volume":"32","author":[{"given":"Jessica Lisa","family":"Littau","sequence":"first","affiliation":[{"name":"Institute of Neuropathology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Velilla","sequence":"additional","affiliation":[{"name":"Neuroscience Group of Antioquia University of Antioquia  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