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For years, neuroscientists have puzzled over how two abnormal proteins, called amyloid and tau, accumulate in the brain and damage it to cause Alzheimer's disease (AD). Which one is the driving force behind dementia? The answer: both of them, according to a new study by researchers at the Douglas Mental Health University Institute.

In the journal Molecular Psychiatry, the team led by Dr. Pedro Rosa-Neto, a clinician scientist at the Douglas and assistant professor of Neurology, Neurosurgery and Psychiatry at 看片视频 University, reports for the first time evidence that the interaction between amyloid and tau proteins drives brain damage in cognitively intact individuals.

鈥漌e specifically found that both proteins mutually enhance their individual toxic effects and cause a brain dysfunction considered to be a signature of AD. This finding challenges previous polarized theories that a single protein abnormality was the major driving force of disease progression,鈥� explains Dr. Rosa-Neto, whose team is part of the CIUSSS de l鈥橭uest-de-l鈥櫭巐e-de-Montr茅al research network.

Toward new therapeutic strategies

This research also points toward new therapeutic strategies to mitigate the progression of AD.

鈥漊ntil now, therapeutic clinical trials have targeted a single pathological process. Our result paves the way for new therapeutic strategies for prevention or stabilization of AD. For example, combination therapies should be used simultaneously against both amyloid and tau protein accumulation鈥�, says Dr. Tharick A. Pascoal, lead author of the study.

Rosa-Neto鈥檚 team analyzed the performances of 120 cognitively intact individuals over two years (equal gender distribution; average age 75). By measuring amyloid levels using PET scans and tau proteins through cerebrospinal fluid analysis, the researchers were able to identify the patients at risk of brain damage associated with AD.

According to the World Health Organization, Alzheimer鈥檚 disease is the most common cause of dementia, affecting more than 30 million people worldwide in 2015. In 2011, 747聽000 Canadians were living with Alzheimer鈥檚 disease and other forms of dementia, and the combined direct (medical) and indirect (lost earnings) costs of dementia amounted to $33 billion (Alzheimer Society of Canada).

This work was funded by the Canadian Institutes of Health Research, the Alan Tiffin Foundation and the Alzheimer's Association. Individuals聽evaluated in this study聽were part of the Alzheimer鈥檚 disease neuroimaging initiative study.

"Amyloid-尾 and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer鈥檚 disease", Molecular Psychiatry, published online 29聽March聽2016. DOI: 10.1038/mp.2016.37

About the science team of Dr. Pedro Rosa-Neto

Dr. Pedro Rosa-Neto (MD, PhD) is the current deputy director of the PREVENT-AD program and leads the translational neuroimaging laboratory (TNL). The TNL conducts groundbreaking research on quantifying neurodegenerative processes using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) to enable preclinical diagnosis of dementing diseases.

Dr. Serge Gauthier (MD, FRCPC) is a neurologist and a full-time clinician researcher who has been conducting research on dementing disorders at the Douglas Institute since 1990. Dr. Gauthier is the director of the Alzheimer's Disease Research Unit at the 看片视频 Centre for Studies in Aging. In 2015, he was appointed to the Order of Canada for his contributions to advancing our understanding of Alzheimer's disease and dementia, and for fostering the development of research networks in his specialty.

Dr. Tharick Ali Pascoal (MD) is a Brazilian neurologist who is currently conducting PhD studies on the Integrated Program in Neuroscience (IPN) at 看片视频 聽Dr. Pascoal is a recipient of a Stop-AD scholarship. For his thesis, he focuses on in vivo quantification of protein to protein interactions as determinants of dementia using imaging and fluid biomarkers. 聽

About the CIUSSS de l鈥橭uest-de-l鈥櫭巐e-de-Montr茅al

The Centre int茅gr茅 universitaire de sant茅 et de services sociaux (CIUSSS) de l鈥橭uest-de-l鈥櫭巐e-de-Montr茅al is made up of the CSSS de l鈥橭uest-de-l鈥櫭巐e, the CSSS de Dorval-Lachine-LaSalle, St. Mary鈥檚 Hospital, St. Anne鈥檚 Hospital, Douglas Mental Health University Institute, West Montreal Readaptation Centre, Grace Dart Extended Care Centre, and Batshaw Youth and Family Centres.

The Douglas Mental Health University Institute is a world-class institute affiliated with 看片视频 University and the World Health Organization. It treats people suffering from mental illness and offers them both hope and healing. Its teams of specialists and researchers are constantly increasing scientific knowledge, integrating this knowledge into patient care, and sharing it with the community in order to educate the public and eliminate prejudices surrounding mental health.

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Centre int茅gr茅 universitaire de sant茅 et de services sociaux de l鈥橭uest-de-l鈥櫭巐e-de-Montr茅al