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BIOMARKER FOR ALZHEIMER'S RELATED COGNITIVE DEFICITS

Award Number: R43AG026190
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2005
PERIOD OF PERFORMANCE END DATE: 12/31/2005

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BIOMARKER FOR ALZHEIMER'S RELATED COGNITIVE DEFICITS - DESCRIPTION (provided by applicant): The molecular and cellular details underlying Alzheimer's disease (AD) are being defined at an accelerating pace, leading to new therapeutic discovery efforts that target reduction of A-beta or ADDLs (A-beta-derived diffusible ligands), the neurotoxic oligomeric assemblies of A-beta 1-42. Elevated ADDL levels correlate with synaptic dysfunction, and the appearance of ADDLs in brain tissue coincides with cognitive decline in Tg2576 AD mice, a transgenic AD animal model. Recent studies have demonstrated that ADDLs are 70-fold elevated in AD brain tissue, and that ADDLs interfere directly with synaptic function, learning and memory. It is possible that even low levels of ADDLs in serum samples may predict cognitive decline. This proposal aims to develop diagnostic tests that can measure ADDL levels in human fluid and tissue samples. Such tests will help establish a connection between ADDL levels and cognitive deficits. A serum or cerebrospinal fluid (CSF) ADDL diagnostic will be a valuable tool for identification of relevant patients with AD and mild cognitive impairment (MCI) as clinical trial participants. For testing of drugs that lower Abeta or ADDL levels, a quantitative ADDL diagnostic will be pivotal to establish that symptomatic efficacy parallels a drop in ADDL levels. Acumen and its collaborators have developed sensitive ELISA-based technology that detects ADDLs at femtomolar levels in human CSF samples. Experiments with ADDL-selective antibodies have provided preliminary evidence that ADDLs are present in plasma samples from Tg2576 mice and Down's syndrome patients. These encouraging preliminary data serve as the foundation for this proposal to: 1) optimize ADDL detection capabilities, 2) optimize an ADDL diagnostic assay format suitable as a reference test for human clinical samples, and 3) validate the hypothesis that ADDL levels correlate with human cognitive deficits. Objectives one and two will be the focus of Phase I, and objective three will be the focus of Phase II.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2005 ( Subtotal = $145,774 )
2005	2005	ACUMEN PHARMACEUTICALS INC	385 OYSTER POINT BOULEVARD	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Aging Research	000	1	7/29/2005	NEW	$145,774
														Subtotal = $145,774

Grand Total All Awards = $145,774

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BIOMARKER FOR ALZHEIMER'S RELATED COGNITIVE DEFICITS

Award Number: R43AG026190

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2005

PERIOD OF PERFORMANCE END DATE: 12/31/2005

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