MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration.
BACKGROUND
Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry.


OBJECTIVE
To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects.


METHODS
Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE).


RESULTS
The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease.


CONCLUSIONS
There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.
Whitwell
Jennifer L
JL
Department of Radiology, Mayo Clinic Rochester, Rochester, Minn. 55905, USA.
Jack
Clifford R
CR
Senjem
Matthew L
ML
Parisi
Joseph E
JE
Boeve
Bradley F
BF
Knopman
David S
DS
Dickson
Dennis W
DW
Petersen
Ronald C
RC
Josephs
Keith A
KA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016875:tau Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016875:tau Proteins