Clinicopathological and genetic correlates of frontotemporal lobar degeneration and corticobasal degeneration.
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.
Lladó
Albert
A
Service of Neurology, Hospital Clínic and Institut d'Investigació, Biomèdica August Pi i Sunyer, Barcelona, Spain.
Sánchez-Valle
Raquel
R
Rey
Maria Jesús
MJ
Ezquerra
Mario
M
Tolosa
Eduardo
E
Ferrer
Isidro
I
Molinuevo
José Luis
JL
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D018888:Aphasia, Primary Progressive / Q000175:diagnosis* / Q000235:genetics; D001706:Biopsy; D004252:DNA Mutational Analysis; D003704:Dementia / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005817:Genetic Counseling / Q000592:standards; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; D016875:tau Proteins