gms | German Medical Science

Background: Frontotemporal lobar degenerations (FTLDs) are clinically and neuropathlogically heterogeneous (McKhan et al., 1984, 2001) and may account for ~10% of dementias. A proportion of patients who meet the NINCDS-ADRDA criteria for AD have FTLD confirmed at autopsy, with or without concomitant AD.

Sample: Forty-eight cases of autopsy-confirmed FTLD were compared with 27 autopsy-confirmed AD cases at Alzheimer´s Disease Research Center Neuropathology Core and Betty Martz Laboratory for Neurodegenerative Research at Washington University, St. Louis, MO, USA.

Neuropathological assessment: Routine assessment was performed as described elsewhere (Liscic et al., 2007). The assessment of AD was based on the criteria of Khachaturian, the CERAD, and the NIA-Reagan Institute criteria. Alzheimer's disease-type changes were rated according to either neurofibrillary tangle stage ≥ IV or ß-amyloid stage C of Braak and Braak (1991), even in the presence of other pathology.

APOE genotyping: Genomic DNA was extracted from fresh-frozen brain or antemortem blood samples.

Results: Of 48 FTLD cases, 17 were tauopathies: CBD (n=9), FTLD-parkinsonism linked to chromosome 17 (n=3), Pick disease (n=2), PSP (n=1), AGD (n=1), and tangle-only dementia (n=1). However, most FTLD cases were characterized by ubiquitin-positive, tau negative inclusions (FTLD-MND). Co-existing hippocampal AD-type pathology was present in 11/48 (23%) of FTLD individuals. From 6/11 individuals with additional AD-type pathology, 2 bore at least one copy of APOE ε4 allele.

Conclusion: FTLD-MND is the most frequent FTLD in our study, but less common entities, such as AGD may be present clinically and should be considered as part of the neuropathologic spectrum of FTLDs. The presence of histopathological AD in almost one fourth of individuals with FTLD may resemble the overlap of FTLD and AD clinical phenotypes.