Researchers crack degeneration process that leads to Alzheimer's

A research group led by Dr. A. Claudio Cuello of McGill University's Faculty of Medicine, Dept. of Pharmacology and Therapeutics, has uncovered a critical process in understanding the degeneration of brain cells sensitive to Alzheimer's disease (AD). The study, published in the February issue of the Journal of Neuroscience, suggests that this discovery could help develop alternative AD therapies.

A breakdown in communication between the brain's is thought to contribute to the and cognitive failure seen in people with AD. The likely suspect is NGF (), a molecule responsible for generating signals that maintain healthy cholinergic neurons – a subset of that are particularly sensitive to AD – throughout a person's lifetime. Oddly, scientists had never been able to find anything wrong with this molecule to explain the degeneration of cholinergic neurons in patients with AD.

This new study, however, has elucidated the process by which NGF is released in the brain, matures to an active form and is ultimately degraded. The researchers were also able to determine how this process is altered in AD. The group demonstrated that treatment of healthy adult rats with a drug that blocks the maturation of active NGF leads to AD-like losses of cholinergic functional units, which result in cognitive impairments. By contrast, when treated with a drug to prevent degradation of active NGF, the numbers of cholinergic contacts increased significantly.

"Part of the difficulty in understanding this pathway has been due to the technical challenges associated with differentiating the active and inactive forms of NGF," explained Dr. Simon Allard, the study's lead author and a postdoctoral fellow at McGill. "Our proposed manipulations are different from existing therapies as they aim to protect neurons from degeneration."

The authors suggest that these findings may lead to pharmacological treatments that could delay the progression of Alzheimer's disease. "This discovery should help design alternative therapies," said Dr. Cuello, a Charles E. Frosst / Merck Chair.

Related Stories

Researchers testing gene therapy for Alzheimer's disease

Jan 07, 2010

University Hospitals Case Medical Center is one of 12 sites conducting the first Phase 2 clinical trial of a gene therapy for Alzheimer's disease (AD). The study uses a viral-based gene transfer system called CERE-110, which ...

Growth factor protects key brain cells in Alzheimer's models

Feb 08, 2009

Memory loss, cognitive impairment, brain cell degeneration and cell death were prevented or reversed in several animal models after treatment with a naturally occurring protein called brain-derived neurotrophic factor (BDNF). ...

New target for Alzheimer's disease identified

May 07, 2008

Alzheimer’s disease (AD) is an incurable disease that is increasing in prevalence and will increase even more rapidly as the Baby Boom generation enters the age of highest risk. The available AD drugs are only partially ...

Recommended for you

Quality of life and Alzheimer's assessed

Aug 19, 2014

A decline in cognitive functions does not necessarily mean lower health-related quality of life for people diagnosed with mild to moderate Alzheimer's disease, new research suggests.

DNA methylation involved in Alzheimer's disease

Aug 17, 2014

A new study led by researchers at Brigham and Women's Hospital (BWH) and Rush University Medical Center, reveals how early changes in brain DNA methylation are involved in Alzheimer's disease. DNA methylation ...

User comments