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Arch Neurol. 2009 Dec;66(12):1483-8. doi: 10.1001/archneurol.2009.277.

Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome.

Author information

1
Drexel University College of Medicine Philadelphia, Philadelphia, Pennsylvania 19102, USA. clippa@drexelmed.edu

Abstract

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.

DESIGN:

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.

PMID:
20008652
PMCID:
PMC2864642
DOI:
10.1001/archneurol.2009.277
[Indexed for MEDLINE]
Free PMC Article

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