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ARRA Investments in Alzheimer’s Disease Research

Public Health Burden
Alzheimer's disease (AD) is a progressive, at present irreversible brain disease that slowly destroys memory and thinking skills, and eventually the ability to carry out even the simplest tasks of daily living. Based on current trends, the number of Americans affected by AD is expected to increase substantially as the population ages.  In addition to the research described below, ARRA-supported research is continuing efforts to understand trends in cognitive impairment and dementia in the United States.1

Basic Research
Basic research to better understand the development and progression of AD will lay the foundation for new prevention and treatment interventions.  ARRA-supported researchers are:
  • Investigating how AD and vascular disease might adversely affect one other.  Findings may suggest strategies for preventing dementia.2
  • Investigating how amyloid, a protein that is implicated in AD pathogenesis, contributes to the formation of clots in the brain and blood vessels.3
  • Examining how energy metabolism influences brain aging by looking for correlations among brain imaging patterns, dementia, and metabolic measures in aging and in people with AD. 4
Genetic and Other Risk Factors
The ability to identify individuals at risk for AD is increasingly important as preventive interventions are developed for testing and as we learn more about how those at risk may be able to reduce their odds of developing the disease.  ARRA-supported investigators are:
  • Using genome-wide association studies to compare the entire genomes of individuals with and without the disease to identify potential genetic risk factors for cognitive decline and AD. 5
  • Investigating whether or not changes to the brain “histone code” mediate the effect of life experiences on the development of age-related cognitive decline and AD.  Histones are specialized proteins involved in packaging DNA. 6
  • Exploring the association of AD with vascular risk factors (e.g., blood pressure), markers of inflammation, and racial differences.7
Biomarkers for Detection and Diagnosis
Research suggests that the earliest AD pathology begins to develop in the brain long before clinical symptoms yield a diagnosis.  Therefore, it is critical that we find a way to detect signs of the disease as early as possible so that we can test interventions and, ultimately, treat the disease as early as we can.  ARRA-supported investigators are:
  • Building on the highly successful AD Neuroimaging Initiative (ADNI), to determine the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of mild cognitive impairment (MCI), often a precursor condition to AD.8
  • Identifying best practices for collecting samples of cerebrospinal fluid and analyzing them for protein biomarkers and attempting to identify AD biomarkers in cerebrospinal fluid before symptoms appear.9
  • Comparing the effectiveness of brain imaging and blood biomarkers to diagnose AD.10
Possible Prevention and Treatment Strategies
ARRA-supported investigators are:
  • Closely following participants in the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) to elucidate the long-term effect of naproxen and other NSAIDS on cognitive health.11
  • Evaluating the effects of exercise in combination with two dietary supplements – the omega 3 fatty acid DHA and curcumin – on AD biomarkers and cognition in an animal model. 12
  • Testing whether blocking a key inflammation pathway alleviates the consequences of high cholesterol on the brain of mouse models of AD.  High cholesterol is believed to increase the risk of AD by triggering inflammation pathways that ultimately damage brain cells.13
  • Studying the drug methylphenidate to treat apathy, which is one of the most common behavioral symptoms of AD and one for which there is currently no effective treatment.14
  • Studying the use of the outer shell, or capsid, of certain viruses to carry protective or therapeutic molecules into the brains of AD patients.  This early work is being carried out in a mouse model of AD, but if successful, it could have broad application in neurodegenerative disease.15
  • Studying whether compounds that manipulate the histone code might prove therapeutic for AD and other neurological disorders.16

  1. 1RC2AG036554-01 -- National Trends in Brain Health: A Follow-Up Study of CIND and Dementia in the U.S. -- David Weir (MI)
  2. 1F32AG031620-01A2 -- Role of Microvascular Lesions in Alzheimer's Disease -- Nozomi Nishimura (NY)
  3. 2R01NS050537-06 -- Role of Fibrin in Alzheimer’s Disease -- Sidney Strickland (NY)
  4. 3K23NS058252-04S1 -- Energy Metabolism and Brain Changes with Age and Alzheimer's Disease. -- Jeffrey Burns (KS)
  5. 2R01AG016208-10A2, --GenomicSearchforSusceptibilitytoAlzheimerDisease--AlisonGoate(MO);1RC2AG036528-01, --GenomeWideAssociateAnalysisofAlzheimer’sDisease--GerardSchellenberger(PA);1RC2AG036650-01 -- Genome-Wide Association Study of Cognitive Decline Among Older African Americans -- Denis A. Evans, Jill R. Murrell, and Philip De Jager (IL)
  6. 1RC2AG036547-01 -- Cognitive Decline and Dementia: Life Experiences and the Brain Histone Epigenome -- David Bennett (IL)
  7. 2R01AG011101-16 -- Risk Factors for Incident Alzheimer's Disease in a Biracial Community -- Denis Evans (IL)
  8. 1RC2AG036535-01 -- Amyloid Imaging, VMCI, and Analysis for ADNI -- Michael Weiner (CA)
  9. 1RC2NS069502-01, --AdvancingProteomicAnalysisofCSFinNervousSystemDiseases.--HowardSchulman(NC);1RC1AG035654-01 -- LC-MS/MS Analysis of CSF and Antecedent Biomarkers of AD -- David Holtzman (MO)
  10. 1RC1AG036208-01 -- Comparative Effectiveness of Brain Imaging and Blood Biomarkers in Alzheimer’s Disease -- Orly Lazarov (IL)
  11. 2U01AG015477-06A2 -- Prevention of Alzheimer Dementia and Cognitive Decline -- John Breitner (WA)
  12. 1RC1AG035878-01 -- Diet and Exercise (DE) Program for Alzheimer Prevention -- Gregory Cole (contact) and Sally Ann Frautschy (CA)
  13. 1R21NS063183-01A1 -- Atherogenic Induction of Neuroinflammation -- Naryan Bhat (SC)
  14. 1R01AG033032-01 -- Apathy in Alzheimer's Disease Methylphenidate Trial -- Jacobo Mintzer, Paul Rosenberg, and Krista Lanctot (SC)
  15. 1RC1AG036265-01 -- Peripherally Administered Gene Therapy for Alzheimer's -- Bradley Hyman (MA)
  16. 1RC1AG035711-01 -- HDAC1 Activating Compounds as Therapeutics for Neurodegenerative Disorders. Li-Huei Tsai (MA)

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