Abstract

The long term objective is to elucidate the biochemical properties of cholinesterases in the plaques and tangles of Alzheimer's disease. Anatomical, pathological, histochemical, biochemical, immunohistochemical and ultrastructural methods will be used to identify the unique properties of plaque and tangle-bound cholinesterases. This is and important objective because recent observations have revealed a selective and universal enhancement of cholinesterase activity in all plaques and tangles. Furthermore, it appears that these cholinesterases are different from the cholinesterases may thus play an important role in the pathogenesis of Alzheimer's disease. As part of this research, cholinesterase inhibitors that are optimally suited to inhibit the type of cholinesterases associated with plaques and tangles will be sought and identified. Cholinesterase inhibitors with this type of activity profile may be more effective than currently available substances for the treatment of Alzheimer's disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005134-09
Application #
3790065
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Jacobs, Heidi I L; Hedden, Trey; Schultz, Aaron P et al. (2018) Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci 21:424-431
Rieckmann, Anna; Johnson, Keith A; Sperling, Reisa A et al. (2018) Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging. Proc Natl Acad Sci U S A 115:10160-10165
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211
Martinez-Ramirez, Sergi; van Rooden, Sanneke; Charidimou, Andreas et al. (2018) Perivascular Spaces Volume in Sporadic and Hereditary (Dutch-Type) Cerebral Amyloid Angiopathy. Stroke 49:1913-1919
Qian, Winnie; Fischer, Corinne E; Schweizer, Tom A et al. (2018) Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease. Curr Alzheimer Res 15:187-194
Putcha, Deepti; McGinnis, Scott M; Brickhouse, Michael et al. (2018) Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy. Cortex 106:36-46
Qian, Jing; Chiou, Sy Han; Maye, Jacqueline E et al. (2018) Threshold regression to accommodate a censored covariate. Biometrics :
Mordes, Daniel A; Prudencio, Mercedes; Goodman, Lindsey D et al. (2018) Dipeptide repeat proteins activate a heat shock response found in C9ORF72-ALS/FTLD patients. Acta Neuropathol Commun 6:55
Gallagher, Damien; Kiss, Alex; Lanctot, Krista et al. (2018) Depression and Risk of Alzheimer Dementia: A Longitudinal Analysis to Determine Predictors of Increased Risk among Older Adults with Depression. Am J Geriatr Psychiatry 26:819-827
Makaretz, Sara J; Quimby, Megan; Collins, Jessica et al. (2018) Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. J Neurol Neurosurg Psychiatry 89:1024-1031

Showing the most recent 10 out of 966 publications