Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations
2008

Heterogeneity in Dementia Linked to Presenilin Mutations

Sample size: 10 publication 10 minutes Evidence: moderate

Author Information

Author(s): Chera L Maarouf, Ian D Daugs, Salvatore Spina, Ruben Vidal, Tyler A Kokjohn, Lyle R Patton, Walter M Kalback, Dean C Luehrs, Douglas G Walker, Eduardo M Castaño, Thomas G Beach, Bernardino Ghetti, Alex E Roher

Primary Institution: The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, AZ, USA

Hypothesis

How do different presenilin mutations affect the biochemical and neuropathological profiles in familial Alzheimer's disease?

Conclusion

Missense mutations in presenilin genes lead to diverse biochemical and clinical manifestations in dementia.

Supporting Evidence

  • Four of the ten cases showed a significant increase in Aβ40 compared to Aβ42.
  • Different presenilin mutations resulted in varied levels of amyloid deposits and neurofibrillary tangles.
  • Significant heterogeneity was observed in the processing of Notch-1, N-cadherin, and Erb-B4 among the mutations.

Takeaway

This study looked at how different changes in a gene related to Alzheimer's can cause different problems in the brain, making each person's experience with dementia unique.

Methodology

The study compared the histopathological and biochemical profiles of ten familial Alzheimer's disease cases with different presenilin mutations.

Limitations

The study's sample size is small and may not represent the full spectrum of presenilin mutations.

Participant Demographics

Five females and five males with an average age at death of 53 years for the PSEN group.

Digital Object Identifier (DOI)

10.1186/1750-1326-3-20

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