Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome.
OBJECTIVE
To assess the transactive response DNA-binding protein 43 (TDP-43) burden in familial forms of Alzheimer disease (FAD) and Down syndrome (DS) to determine whether TDP-43 inclusions are also present.


METHODS
Using standard immunohistochemical techniques, we examined brain tissue samples from 42 subjects with FAD and 14 with DS.


RESULTS
We found pathological TDP-43 aggregates in 14.0% of participants (6 of 42 and 2 of 14 participants with FAD and DS, respectively). In both FAD and DS, TDP-43 immunoreactivity did not colocalize with neurofibrillary tangles. Occasionally participants with FAD or DS had TDP-43-positive neuropil threads or dots. Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions. A similar distribution of TDP-43 inclusions is seen in sporadic Alzheimer disease, but it differs from that seen in amyotrophic lateral sclerosis and frontotemporal dementia.


CONCLUSIONS
Transactive response DNA-binding protein 43 pathology occurs in FAD and DS, similar to that observed in sporadic Alzheimer disease. Thus, pathological TDP-43 may contribute the cognitive impairments in familial and sporadic forms of Alzheimer disease.
Lippa
Carol F
CF
Drexel University College of Medicine Philadelphia, Philadelphia, Pennsylvania 19102, USA. clippa@drexelmed.edu
Rosso
Andrea L
AL
Stutzbach
Lauren D
LD
Neumann
Manuela
M
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D015415:Biomarkers; D004268:DNA-Binding Proteins