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

Topic: Brain proteins, microglia and lab models

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.

Key findings

• 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).
• Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions.

Why it matters

In brain tissue from 42 people with familial Alzheimer's disease and 14 with Down syndrome, pathological TDP-43 aggregates were found in 14.0% of participants, most often in the amygdala and hippocampus with none in neocortical regions. The authors conclude that TDP-43 pathology may contribute to cognitive impairment in familial and sporadic Alzheimer's disease.

Study details

• Participants42
• Effect size14.0%
• Evidence strengthLow

Limitations

The sample sizes are small (42 people with familial Alzheimer's and 14 with Down syndrome), so the 14% figure comes from a small number of actual cases (6 and 2, respectively) and should be interpreted cautiously.

Read the original

• DOI: 10.1001/archneurol.2009.277
• PubMed: 20008652
• Original source →
• Free full text: Archives of Neurology →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{lippa2009-20008652,
  author  = {Lippa, C. F. and Rosso, A. L. and Stutzbach, L. D. and Neumann, M. and Lee, V. M. and Trojanowski, J. Q.},
  title   = {{Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome}},
  journal = {Archives of neurology},
  year    = {2009},
  doi     = {10.1001/archneurol.2009.277},
  pmid    = {20008652},
  url     = {https://doi.org/10.1001/archneurol.2009.277}
}

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