{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:26:36Z","timestamp":1792070796161,"version":"4.4.0"},"reference-count":24,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:p>Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer\u2019s disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer\u2019s disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.<\/jats:p>","DOI":"10.3233\/jad-201085","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T12:37:12Z","timestamp":1605616632000},"page":"25-30","source":"Crossref","is-referenced-by-count":11,"title":["Neuropathological Alzheimer\u2019s Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes"],"prefix":"10.1177","volume":"79","author":[{"given":"Emanuela","family":"Maderna","sequence":"first","affiliation":[{"name":"Neurology 5 - Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vison\u00e0","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Bolcato","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Redaelli","sequence":"additional","affiliation":[{"name":"Neurology 5 - Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Caroppo","sequence":"additional","affiliation":[{"name":"Neurology 5 - Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Montalbetti","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Giaccone","sequence":"additional","affiliation":[{"name":"Neurology 5 - Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Osculati","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy"},{"name":"IRCCS Mondino Foundation, Pavia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-201085_ref1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1212\/WNL.32.3.329","article-title":"Nasu-Hakola\u2019s disease: An example of geographic neuropathology?","volume":"32","author":"Matsushita","year":"1982","journal-title":"Neurology"},{"key":"10.3233\/JAD-201085_ref2","first-page":"1","article-title":"Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia","volume":"232","author":"Hakola","year":"1972","journal-title":"Acta Psychiatr Scand Suppl"},{"key":"10.3233\/JAD-201085_ref3","first-page":"109","article-title":"Hereditary diseases in Finland; rare flora in rare soul","volume":"5","author":"Norio","year":"1973","journal-title":"Ann Clin Res"},{"key":"10.3233\/JAD-201085_ref4","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1136\/jmg.30.10.857","article-title":"Disease gene mapping in isolated human populations: The example of Finland","volume":"30","author":"De la Chapelle","year":"1993","journal-title":"J Med Genet"},{"key":"10.3233\/JAD-201085_ref5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1440-1789.2010.01127.x","article-title":"Nasu-Hakola disease: The first case reported by Nasu and review","volume":"30","author":"Kaneko","year":"2010","journal-title":"Neuropathology"},{"key":"10.3233\/JAD-201085_ref6","first-page":"171","article-title":"Nasu-Hakola disease: A rare entity in Italy. 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