Current concepts in the pathogenesis of Alzheimer's disease - PubMed (original) (raw)
Review
Current concepts in the pathogenesis of Alzheimer's disease
D B Carr et al. Am J Med. 1997.
Abstract
Alzheimer's disease (AD) affects a large proportion of the increasingly aging population of this country, with prevalence rates as high as 47% for those >85 years old and a total annual cost approaching $70 billion. There is no currently validated test for detection of dementia of the Alzheimer type (DAT). Because of this and the insidious onset of the disease, the diagnosis may be missed by primary care physicians. Cerebral extracellular beta-amyloid deposition as senile plaques and intraneuronal neurofibrillary tangles appear to represent critical processes in the development of AD; however, whether and the extent to which these may also occur in nondemented aging is uncertain. Tangles occur primarily in medial temporal lobe structures (hippocampus, entorhinal cortex, and amygdala), and tangle density correlates with dementia severity. Plaques are diffusely distributed throughout the cerebral cortex, and are the neuropathologic hallmark of the disease. Aging is the primary risk factor for AD. After controlling for differential life expectancy, female sex still appears to be an additional risk factor. There may be a genetic component, in some cases based on family and twin studies. Allelic variation in the apolipoprotein E (Apo E) gene located on chromosome 19 represents another important risk factor. However, the diversity of gene mutations apparently responsible for the various forms of AD suggest that the disease is genetically heterogeneous. AD may be conceptualized as an imbalance between neuronal injury and repair. Oxygen free radicals may be involved in the cross-linking process of beta-amyloid aggregation, and antioxidants may represent a potential intervention. There may be a role for heavy metals in the pathogenesis of AD, but this remains controversial. Work continues toward possibly a cure or prevention, but more likely palliation, of AD, and the results of trials of anti-inflammatory agents, estrogen, and antioxidant therapy are anticipated in the near future.
Comment in
- The role of estrogen in the treatment and prevention of dementia: introduction.
Birge SJ. Birge SJ. Am J Med. 1997 Sep 22;103(3A):1S-2S. doi: 10.1016/s0002-9343(97)00263-5. Am J Med. 1997. PMID: 9344400 No abstract available.
Similar articles
- The apolipoprotein E allele epsilon 4 does not correlate with the number of senile plaques or neurofibrillary tangles in patients with Alzheimer's disease.
Landén M, Thorsell A, Wallin A, Blennow K. Landén M, et al. J Neurol Neurosurg Psychiatry. 1996 Oct;61(4):352-6. doi: 10.1136/jnnp.61.4.352. J Neurol Neurosurg Psychiatry. 1996. PMID: 8890772 Free PMC article. - Characterizing Apolipoprotein E ε4 Carriers and Noncarriers With the Clinical Diagnosis of Mild to Moderate Alzheimer Dementia and Minimal β-Amyloid Peptide Plaques.
Monsell SE, Kukull WA, Roher AE, Maarouf CL, Serrano G, Beach TG, Caselli RJ, Montine TJ, Reiman EM. Monsell SE, et al. JAMA Neurol. 2015 Oct;72(10):1124-31. doi: 10.1001/jamaneurol.2015.1721. JAMA Neurol. 2015. PMID: 26302353 Free PMC article. - Alzheimer's disease.
De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. De-Paula VJ, et al. Subcell Biochem. 2012;65:329-52. doi: 10.1007/978-94-007-5416-4_14. Subcell Biochem. 2012. PMID: 23225010 Review. - Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease.
Morris JC, Storandt M, McKeel DW Jr, Rubin EH, Price JL, Grant EA, Berg L. Morris JC, et al. Neurology. 1996 Mar;46(3):707-19. doi: 10.1212/wnl.46.3.707. Neurology. 1996. PMID: 8618671 - Alzheimer's disease.
Turner RS. Turner RS. Semin Neurol. 2006 Nov;26(5):499-506. doi: 10.1055/s-2006-951622. Semin Neurol. 2006. PMID: 17048151 Review.
Cited by
- Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats.
Khalili M, Hamzeh F. Khalili M, et al. Iran Biomed J. 2010 Jan-Apr;14(1-2):59-65. Iran Biomed J. 2010. PMID: 20683499 Free PMC article. - Role of Withaferin A and Its Derivatives in the Management of Alzheimer's Disease: Recent Trends and Future Perspectives.
Das R, Rauf A, Akhter S, Islam MN, Emran TB, Mitra S, Khan IN, Mubarak MS. Das R, et al. Molecules. 2021 Jun 17;26(12):3696. doi: 10.3390/molecules26123696. Molecules. 2021. PMID: 34204308 Free PMC article. Review. - Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits.
Ronald JA, Chen Y, Bernas L, Kitzler HH, Rogers KA, Hegele RA, Rutt BK. Ronald JA, et al. Brain. 2009 May;132(Pt 5):1346-54. doi: 10.1093/brain/awp031. Epub 2009 Mar 17. Brain. 2009. PMID: 19293239 Free PMC article. - Galantamine: a review of its use in Alzheimer's disease.
Scott LJ, Goa KL. Scott LJ, et al. Drugs. 2000 Nov;60(5):1095-122. doi: 10.2165/00003495-200060050-00008. Drugs. 2000. PMID: 11129124 Review. - Economic considerations in the management of Alzheimer's disease.
Zhu CW, Sano M. Zhu CW, et al. Clin Interv Aging. 2006;1(2):143-54. doi: 10.2147/ciia.2006.1.2.143. Clin Interv Aging. 2006. PMID: 18044111 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical