Alzheimer Disease and Its Growing Epidemic: Risk Factors, Biomarkers, and the Urgent Need for Therapeutics

Overview

Journal Neurol Clin

Specialty Neurology

Date 2016 Oct 11

PMID 27720002

Citations 66

Authors

Richard A Hickman

Arline Faustin

Thomas Wisniewski

Affiliations

Soon will be listed here.

Abstract

Alzheimer disease (AD) represents one of the greatest medical challenges of this century; the condition is becoming increasingly prevalent worldwide and no effective treatments have been developed for this terminal disease. Because the disease manifests at a late stage after a long period of clinically silent neurodegeneration, knowledge of the modifiable risk factors and the implementation of biomarkers is crucial in the primary prevention of the disease and presymptomatic detection of AD, respectively. This article discusses the growing epidemic of AD and antecedent risk factors in the disease process. Disease biomarkers are discussed, and the implications that this may have for the treatment of this currently incurable disease.

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References

Hellstrom-Lindahl E, Ravid R, Nordberg A . Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels. Neurobiol Aging. 2006; 29(2):210-21. DOI: 10.1016/j.neurobiolaging.2006.10.010. View

Goldstein L, Fisher A, Tagge C, Zhang X, Velisek L, Sullivan J . Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med. 2012; 4(134):134ra60. PMC: 3739428. DOI: 10.1126/scitranslmed.3003716. View

Turner A, Fisk L, Nalivaeva N . Targeting amyloid-degrading enzymes as therapeutic strategies in neurodegeneration. Ann N Y Acad Sci. 2005; 1035:1-20. DOI: 10.1196/annals.1332.001. View

. Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. Neurobiol Aging. 1997; 18(4 Suppl):S1-2. View

Langlois J, Rutland-Brown W, Wald M . The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006; 21(5):375-8. DOI: 10.1097/00001199-200609000-00001. View

Yan P, Hu X, Song H, Yin K, Bateman R, Cirrito J . Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem. 2006; 281(34):24566-74. DOI: 10.1074/jbc.M602440200. View

Fratiglioni L, Paillard-Borg S, Winblad B . An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 2004; 3(6):343-53. DOI: 10.1016/S1474-4422(04)00767-7. View

Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R . Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997; 278(16):1349-56. View

Gentleman S, Nash M, Sweeting C, Graham D, Roberts G . Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett. 1993; 160(2):139-44. DOI: 10.1016/0304-3940(93)90398-5. View

10.

Fleminger S, Oliver D, Lovestone S, Rabe-Hesketh S, GIORA A . Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry. 2003; 74(7):857-62. PMC: 1738550. DOI: 10.1136/jnnp.74.7.857. View

11.

Spinney L . Alzheimer's disease: The forgetting gene. Nature. 2014; 510(7503):26-8. DOI: 10.1038/510026a. View

12.

Deane R, Sagare A, Zlokovic B . The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Curr Pharm Des. 2008; 14(16):1601-5. PMC: 2895311. DOI: 10.2174/138161208784705487. View

13.

Ferri C, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M . Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366(9503):2112-7. PMC: 2850264. DOI: 10.1016/S0140-6736(05)67889-0. View

14.

Arvanitakis Z, Wilson R, Bienias J, Evans D, Bennett D . Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004; 61(5):661-6. DOI: 10.1001/archneur.61.5.661. View

15.

. 2015 Alzheimer's disease facts and figures. Alzheimers Dement. 2015; 11(3):332-84. DOI: 10.1016/j.jalz.2015.02.003. View

16.

Edland S, Rocca W, Petersen R, Cha R, Kokmen E . Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn. Arch Neurol. 2002; 59(10):1589-93. DOI: 10.1001/archneur.59.10.1589. View

17.

Kalaria R, Maestre G, Arizaga R, Friedland R, Galasko D, Hall K . Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 2008; 7(9):812-26. PMC: 2860610. DOI: 10.1016/S1474-4422(08)70169-8. View

18.

Shively S, Scher A, Perl D, Diaz-Arrastia R . Dementia resulting from traumatic brain injury: what is the pathology?. Arch Neurol. 2012; 69(10):1245-51. PMC: 3716376. DOI: 10.1001/archneurol.2011.3747. View

19.

Ferguson P, Smith G, Wannamaker B, Thurman D, Pickelsimer E, Selassie A . A population-based study of risk of epilepsy after hospitalization for traumatic brain injury. Epilepsia. 2009; 51(5):891-8. DOI: 10.1111/j.1528-1167.2009.02384.x. View

20.

Reitz C, Brayne C, Mayeux R . Epidemiology of Alzheimer disease. Nat Rev Neurol. 2011; 7(3):137-52. PMC: 3339565. DOI: 10.1038/nrneurol.2011.2. View