Mechanism linked to initiation of plaques in Alzheimer’’s identified

December 25th, 2008 - 2:40 pm ICT by ANI  

Washington, Dec 25 (ANI): Scientists from Northwestern University Feinberg School of Medicine have identified a molecular mechanism that triggers initiation of plaques in Alzheimer’’s brain.

Alzheimers disease is characterized by accumulation and deposition of sticky clumps of Aa protein. It is generated from amyloid precursor protein (APP) by BACE1 enzyme.

BACE1 was linked to cellular stress responses in the brain. The AD brain exhibits impaired energy metabolism (a stressful situation) and it has been suggested that diminished cerebral use of glucose and oxygen may be an early event in AD pathogenesis

During the study, Dr. Robert Vassar and his colleagues explored the link between energy inhibition and AD pathogenesis.

“We have shown previously, using a pharmacological model of energy metabolism inhibition in pre-plaque transgenic mice with an excess of APP, that BACE1 and Aa levels are elevated in the brain,” said Dr. Vassar.

They expanded on their previous work by using glucose deprivation to examine the molecular mechanisms underlying elevated BACE1 levels in response to energy inhibition.

They found that glucose deprivation caused an increase in BACE1 levels and led to the phosphorylation of the stress-inducible translation initiation factor, eIF2.

Direct phosphorylation of eIF2 elevated the BACE1 levels and enhanced Aa production, while inhibition of eIF2 phosphorylation prevented energy-deprivation induced increases in BACE1.

The researchers hope that the discovery will help in developing new preventative and disease-modifying therapies for AD, especially those aimed at interrupting pathological Aa-production.

The study appears in journal Neuron. (ANI)

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