Clinicopathological and genetic correlates of frontotemporal lobar degeneration and corticobasal degeneration

• Published in: Journal of neurology Vol. 255; no. 4; pp. 488 - 494
• Main Authors: Lladó, Albert, Sánchez-Valle, Raquel, Rey, Maria Jesús, Ezquerra, Mario, Tolosa, Eduardo, Ferrer, Isidro, Molinuevo, José Luis
• Format: Journal Article
• Language: English
• Published: Darmstadt Steinkopff-Verlag 01.04.2008; Springer; Springer Nature B.V
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; Aphasia, Primary Progressive - diagnosis; Aphasia, Primary Progressive - genetics; Biological and medical sciences; Biopsy; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia - diagnosis; Dementia - genetics; Diagnosis, Differential; DNA Mutational Analysis; Female; Genetic Counseling - standards; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Humans; Inclusion Bodies - genetics; Inclusion Bodies - metabolism; Inheritance Patterns; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Motor Neuron Disease - complications; Motor Neuron Disease - diagnosis; Motor Neuron Disease - genetics; Mutation - genetics; Neurodegenerative Diseases - classification; Neurodegenerative Diseases - diagnosis; Neurodegenerative Diseases - genetics; Neurology; Neuroradiology; Neurosciences; Original Communication; Predictive Value of Tests; tau Proteins - analysis; tau Proteins - genetics; tau Proteins - metabolism; tauopathies; MAPT; corticobasal degeneration; frontotemporal lobar degeneration; Nervous system diseases; Degeneration
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-008-0565-8

Objective To correlate clinical diagnosis and genetic features with different pathological substrates in patients with frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). Methods 32 cases with pathological proven FTLD or CBD were selected. Patients were classified clinically as frontotemporal dementia (FTD), progressive nonfluent aphasia (PNFA), semantic dementia (SD), CBD or FLTD with motor neuron disease (FLTDMND). Coding exons 1 and 9–13 of MAPT and exons 0–12 of the PGRN gene were screened by direct sequencing. Regarding the neuropathological findings, cases were classified as tau-positive, ubiquitinpositive tau-negative (FTLD-U), neuronal intermediate filaments inclusions disease (NIFID), dementia lacking distinctive histology (DLDH) or CBD. Results 17 patients were clinically diagnosed with FTD. Ten showed tau pathology, 3 FTLD-U, 1 NIFID and 3 DLDH. All patients clinically classified as FTLD-MND (6 patients) or SD (3 patients) were FTLD-U. Tau-positive pathology was the substrate of the three patients with PNFA. All three patients classified clinically as CBD presented neuropathologic features of CBD. The three individuals with familial history of early onset FTD and tau-positive pathology carried the P301L mutation in the MAPT gene. One out of 3 cases with FTLD-U and intranuclear inclusions carried a mutation in the PGRN gene. Conclusions We found that pathology underlying sporadic FTD is heterogeneous and not predictable. MAPT mutations and clinical diagnosis of PNFA and CBD were associated with tau-positive pathology. The presence of signs of lower MND and SD correlated with FTLD-U.A genetic study of MAPT is only recommended when familial history of early onset DFT is present.