The cholinergic hypothesis of geriatric memory dysfunction.

T1 - The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits

Alzheimer's disease: a disorder of cortical cholinergic innervation.

Through our partnerships and funded projects, the Alzheimer's Association has been part of every major research advancement over the past 30 years. Our flagship accomplishments include:

T1 - Interactions between the amyloid and cholinergic mechanisms in Alzheimer's disease

Variant of TREM2 Associated with the Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by memory and cognitive loss, the formation of senile plaques containing amyloid-β (Aβ) peptide, degeneration of the cholinergic neurons and the development of neurofibrillary tangles. The build-up of Aβ is considered to be a central feature in the pathogenesis of AD. However, other critical molecular and neurochemical alterations too occur, such as a cholinergic dysfunction. As concerns the pathomechanism of the disease, both the amyloid cascade hypothesis and the cholinergic hypothesis of AD are widely accepted. This review surveys recent in vitro and in vivo experimental evidence relating to these two hypotheses. Bidirectional pathways linking them as regards the cholinergic neurotoxicity of Aβ and the regulatory mechanisms of cholinergic receptor activation or enzyme inhibition in the processing of the amyloid precursor protein are also discussed. Further work is warranted to elucidate the exact effects in the interactions between the cholinergic and amyloid hypotheses of the candidate drugs used in AD therapy.

As researchers began to focus on neurotransmitter imbalances as a cause of Alzheimer's disease (AD), the cholinergic hypothesis was proposed.

The Alzheimer's Association funds independent investigators worldwide through our . Since awarding our first grants in 1982, the Association has grown into the largest nonprofit funder of Alzheimer's research. Over the life of our grants program, we have invested over $405 million in more than 2,600 scientific investigations.

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Stimulate a committed response and federal action. To help document the importance of Alzheimer's as a national health priority, the Association in 2007 released its first edition of Alzheimer's Disease Facts and Figures, a comprehensive annual statistical brief detailing the burden of Alzheimer's and other dementias on individuals, families, local and state government and the nation's health care system. .

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Foster cross-institutional quality and consistency in measuring biomarkers. Investigating levels of key Alzheimer-related proteins in cerebrospinal fluid (CSF) is one of the most active areas of research in the drive to earlier diagnosis. One challenge is that analysis of protein levels in the same sample often varies significantly from institution to institution. To facilitate consistency and move this vital area forward, the Association has funded the Alzheimer's Association QC Program for CSF Biomarkers. Organizations can improve their analytic capabilities by comparing their outcomes to results at reference laboratories in the United States and Europe. .

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Increase clinical studies participants. A major impediment to developing new drugs is recruiting and retaining enough qualified participants. To help inform, mobilize and motivate study participants, the Association has launched Alzheimer's Association TrialMatch®, a user-friendly tool to help prospective participants and physicians identify clinical studies that interest them. .

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An increase in federal research funding is critical to forestall both the loss of life and the financial burden on the nation because today there are no survivors and there is no cure. Since our 1980 founding, the Alzheimer's Association has fulfilled a vital role as a nonprofit force complementing federal and industry initiatives. We work to ensure that our national policy and research agendas reflect the importance of Alzheimer's disease as a leading cause of death and disability, a personally devastating illness, and an emerging health care crisis for employers as well as public and private payers. .