{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:15:22Z","timestamp":1777565722913,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Null<\/jats:italic> mutations in progranulin gene (<jats:italic>GRN<\/jats:italic>) reduce the progranulin production resulting in haploinsufficiency and are tightly associated with tau\u2010negative frontotemporal lobar degeneration with TAR DNA\u2010binding protein 43\u2010positive inclusions (FTLD\u2010TDP). Missense mutations of <jats:italic>GRN<\/jats:italic> were also identified, but their effects are not completely clear, in particular unanswered is the question of what neuropathology they elicit, also considering that their occurrence has been reported in patients with typical clinical features of Alzheimer disease. They describe two fraternal twins carrying the missense <jats:italic>GRN<\/jats:italic> Cys139Arg mutation affected by late\u2010onset dementia and we report the neuropathological study of one of them. Both patients were examined by neuroimaging, neuropsychological assessment and genetic analysis of <jats:italic>GRN<\/jats:italic> and other genes associated with dementia. The brain of one was obtained at autopsy and examined neuropathologically. One sister presented clinical and MRI features leading to the diagnosis of Alzheimer disease. The other underwent autopsy and the brain showed neuropathological hallmarks of Alzheimer disease with abundant A\u03b2\u2010amyloid deposition and Braak stage V of neurofibrillary pathology, in the absence of the hallmark lesions of FTLD\u2010TDP. Their findings may contribute to better clarify the role of progranulin in neurodegenerative diseases indicating that some <jats:italic>GRN<\/jats:italic> mutations, in particular missense ones, may act as strong risk factor for Alzheimer disease rather than induce FTLD\u2010TDP.<\/jats:p>","DOI":"10.1111\/bpa.12480","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T19:17:40Z","timestamp":1482261460000},"page":"72-76","source":"Crossref","is-referenced-by-count":20,"title":["Alzheimer neuropathology without frontotemporal lobar degeneration hallmarks (<scp>TAR DNA<\/scp>\u2010binding protein 43 inclusions) in missense progranulin mutation <scp>C<\/scp>ys139<scp>A<\/scp>rg"],"prefix":"10.1111","volume":"28","author":[{"given":"Veronica","family":"Redaelli","sequence":"first","affiliation":[{"name":"Carlo Besta Neurological Institute IRCCS Foundation Milano 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