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 #
5P50AG005134-08
Application #
3802511
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

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

  Publications

Wang, Tingyan; Qiu, Robin G; Yu, Ming (2018) Predictive Modeling of the Progression of Alzheimer's Disease with Recurrent Neural Networks. Sci Rep 8:9161
DeVos, Sarah L; Corjuc, Bianca T; Commins, Caitlin et al. (2018) Tau reduction in the presence of amyloid-? prevents tau pathology and neuronal death in vivo. Brain 141:2194-2212
Lee, Christopher M; Jacobs, Heidi I L; Marquié, Marta et al. (2018) 18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal. J Alzheimers Dis 62:1691-1702
Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela et al. (2018) Longitudinal associations between different dementia diagnoses and medication use jointly accounting for dropout. Int Psychogeriatr 30:1477-1487
Eftekharzadeh, Bahareh; Daigle, J Gavin; Kapinos, Larisa E et al. (2018) Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer's Disease. Neuron 99:925-940.e7
Emerson, Sarah C; Waikar, Sushrut S; Fuentes, Claudio et al. (2018) Biomarker validation with an imperfect reference: Issues and bounds. Stat Methods Med Res 27:2933-2945
Crum, Jana; Wilson, Jeffrey; Sabbagh, Marwan (2018) Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimers Res Ther 10:104
Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739
Pasi, Marco; Marini, Sandro; Morotti, Andrea et al. (2018) Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy. Stroke 49:207-210
Hopp, Sarah C; Lin, Yang; Oakley, Derek et al. (2018) The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer's disease. J Neuroinflammation 15:269

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