Affiliations: [a]
Neurology 5 - Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| [b] Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy
| [c] Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| [d] IRCCS Mondino Foundation, Pavia
Correspondence:
[*]
Correspondence to: Dr. Giorgio Giaccone, Acting Director, Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Institute, via Celoria 11, 20133 Milano, Italy. Tel.: +39 02 2394 2714; Fax: +39 02 2394 2101; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Note: [2] This work is dedicated to the memory of Professor Antonio Osculati.
Abstract: 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’s 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’s disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.
