Physiological and Pathological Functions of Beta-Amyloid in the Brain and Alzheimer's Disease: A Review

10.4103/CJP.CJP_10_20

Ladislav Volicer

Alzheimer's disease ； amyloid ； palliative care

The Chinese Journal of Physiology

63卷3期（2020 / 06 / 30）

95 - 100

英文

Alzheimer's disease is a major health problem all over the world. The role of beta-amyloid (Aβ) is at the center of investigations trying to discover the disease pathogenesis and to develop drugs for treatment or prevention on Alzheimer's disease. This review summarizes both physiological and pathological functions of Aβ and factors that may participate in the disease development. Known genetic factors are trisomy of chromosome 21, mutations of presenilin 1 and 2, and apolipoprotein E4. Lifetime stresses that increase the risk of development of Alzheimer's disease are described. Another important factor is the level of education, especially of linguistic ability. Lifestyle factors include mental and physical exercise, head injury, social contacts, and diet. All these factors might potentiate the effect of aging on the brain to increase the risk of development of pathological changes. The review summarizes pathological features of Alzheimer brain, Aβ plaques, neurofibrillary tangles composed of hyperphosphorylated tau, and brain atrophy. Consequences of Alzheimer's disease that are reviewed include cognitive deficit, loss of function, and neuropsychiatric symptoms. Because there is no effective treatment, many persons with Alzheimer's disease survive to severe and terminal stages which they may fear. Alzheimer's disease at this stage should be considered a terminal disease for which palliative care is indicated. Importance of advance directives, promoting previous wishes of the person who was developing dementia and who subsequently lost decision-making capacity, and limitations of these directives are discussed. Information in this review is based on author's knowledge and clinical experience that were updated by searches of PubMed.

1. Almeida, SI,da Silva, G,Marques, AS(2019).Home-based physical activity programs for people with dementia: Systematic review and meta-analysis.Gerontologist,60(8),600-608.
2. Azarpazhooh, MR,Avan, A,Cipriani, LE,Munoz, DG,Erfanian, M,Amiri, A(2019).A third of community-dwelling elderly with intermediate and high level of Alzheimer’s neuropathologic changes are not demented: A meta-analysis.Ageing Res Rev,58,101002.
3. Baruch‑Suchodolsky, R,Fischer, B(2009).Aβ40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems.Biochemistry,48,4354-4370.
4. Butterfield, DA,Swomley, AM,Sultana, R(2013).Amyloid ß‑peptide (1-42)-induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression.Antioxid Redox Signal,19,823-835.
5. Cass, SP(2017).Alzheimer’s disease and exercise: A literature review.Curr Sports Med Rep,16,19-22.
6. Castellano, JM,Km, J,Stewart, FR,Jiang, H,DeMattos, RB,Patterson, BW(2011).Human apoE isoforms differentially regulate brain amyloid‑ß peptide clearance.Sci Transl Med,3,89ra57.
7. Cohen‑Mansfield, J,Jensen, B(2008).Assessment and treatment approaches for behavioral disturbances associated with dementia in the nursing home: Self-reports of physicians’ practices.J Am Med Dir Assoc,9,406-413.
8. Corder, EH,Saunders, AM,Strittmatter, WJ,Schmechel, DE,Gaskell, PC,Small, GW(1993).Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.Science,261,921-923.
9. Crowe, M,Andel, R,Pedersen, NL,Johansson, B,Gatz, M(2003).Does participation in leisure activities lead to reduced risk of Alzheimer’s disease? A prospective study of Swedish twins.J Gerontol B Psychol Sci Soc Sci,58,249-255.
10. Fonseca, M,Sola, S,Xavier, J,Dionisio, P,Rodrigues, CP(2013).Amyloid ß peptides promote autophagy‑dependent differentiation of mouse neural stem cells: Aß‑mediated neural differentiation.Mol Neurobiol,48,829-840.
11. Garcia-Osta, A,Alberini, CM(2009).Amyloid beta mediates memory formation.Learn Mem,16,267-272.
12. Gilsanz, P,Quesenberry, CP, Jr.,Mayeda, ER,Glymour, MM,Farias, ST,Whitmer, RA(2019).Stressors in midlife and risk of dementia: The role of race and education.Alzheimer Dis Assoc Disord,33,200-205.
13. Giuffrida, ML,Caraci, F,Pignataro, B,Cataldo, S,De Bona, P,Bruno, V(2009).Beta-amyloid monomers are neuroprotective.J Neurosci,29,10582-10587.
14. Glenner, GG,Wong, CW(1984).Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein.Biochem Biophys Res Commun,120,885-890.
15. Lee, L,Dale, E,Staniszewski, A,Zhang, H,Saeed, F,Sakurai, M(2014).Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer’s disease.Sci Rep,4,7190.
16. Leong, YQ,Ng, KY,Chye, SM,Ling, APK,Koh, RY(2020).Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death.Metab Brain Dis,35,11-30.
17. Luo, Y,Hawver, DB,Iwasaki, K,Sunderland, T,Roth, GS,Wolozin, D(1997).Physiological levels of β‑amyloid peptide stimulate protein kinase C in PC12 cells.Brain Res,769,287-295.
18. McKee, AC,Stern, RA,Nowinski, CJ,Stein, TD,Alvarez, VE,Daneshvar, DH(2013).The spectrum of disease in chronic traumatic encephalopathy.Brain,136,43-64.
19. Moore, S,Evans, LD,Andersson, T,Portelius, E,Smith, J,Dias, TB(2015).APP metabolism regulates tau proteostasis in human cerebral cortex neurons.Cell Rep,11,689-696.
20. Ni, R,Marutle, A,Nordberg, A(2013).Modulation of α7 nicotinic acetylcholine receptor and fibrillar amyloid‑ß interactions in Alzheimer’s disease brain.J Alzheimers Dis,33,841-851.
21. Norton, MC,Smith, KR,Østbye, T,Tschanz, JT,Schwartz, S,Corcoran, C(2011).Early parental death and remarriage of widowed parents as risk factors for Alzheimer disease: The Cache County study.Am J Geriatr Psychiatry,19,814-824.
22. Parihar, MS,Brewer, GJ(2010).Amyloid-ß as a modulator of synaptic plasticity.J Alzheimers Dis,22,741-763.
23. Petersen, RC,Lopez, O,Armstrong, MJ,Getchius, TS,Ganguli, M,Gloss, D(2018).Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.Neurology,90,126-135.
24. Phillips, C.(2017).Lifestyle modulators of neuroplasticity: How physical activity, mental engagement, and diet promote cognitive health during aging.Neural Plast,2017,3589271.
25. Plassman, BL,Havlik, RJ,Steffens, DC,Helms, MJ,Newman, TN,Drosdick, D(2000).Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias.Neurology,55,1158-1166.
26. Prince, M,Ali, GC,Guerchet, M,Prina, AM,Albanese, E,Wu, YT(2016).Recent global trends in the prevalence and incidence of dementia, and survival with dementia.Alzheimers Res Ther,8,23.
27. Qiu, C,Karp, A,von Strauss, E,Winblad, B,Fratiglioni, L,Bellander, T(2003).Lifetime principal occupation and risk of Alzheimer’s disease in the Kungsholmen project.Am J Ind Med,43,204-211.
28. Ricciarelli, R,Fedele, E(2017).The amyloid cascade hypothesis in Alzheimer’s disease: It’s time to change our mind.Curr Neuropharmacol,15,926-935.
29. Scheuner, D,Eckman, C,Jensen, M,Song, X,Citron, M,Suzuki, N(1996).Secreted amyloid β‑protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease.Nature Med,2,864-870.
30. Selkoe, DJ,Hardy, J(2016).The amyloid hypothesis of Alzheimer’s disease at 25 years.EMBO Mol Med,8,595-608.
31. Sharma, AK,Pavlova, ST,Kim, J,Kim, J,Mirica, LM(2013).The effect of Cu2+ and Zn2+ on the Aß42 peptide aggregation and cellular toxicity.Metallomics,5,1529-1536.
32. Sharma, K.(2019).Cholinesterase inhibitors as Alzheimer’s therapeutics (Review).Mol Med Rep,20,1479-1487.
33. Sinha, M,Bhowmick, P,Banerjee, A,Chakrabarti, S(2013).A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage.Free Radic Biol Med,56,184-192.
34. Snowdon, DA,Greiner, LH,Mortimer, JA,Riley, KP,Greiner, PA,Markesbery, WR(1997).Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.JAMA,277,813-817.
35. Snowdon, DA,Kemper, SJ,Mortimer, JA,Greiner, LH,Wekstein, DR,Markesbery, WR(1996).Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study.JAMA,275,528-532.
36. Volicer, L(2016).Fear of dementia.J Am Med Dir Assoc,17,875-878.
37. Volicer, L(2019).Review of programs for persons facing death with dementia.Healthcare,7,62.
38. Volicer, L(2007).Goals of care in advanced dementia: Quality of life, dignity and comfort.J Nutr Health Aging,11,481.
39. Volicer, L(1993).Alzheimer’s disease: Course, management, and the hospice approach.Nurs Home Med,1,31-37.
40. Volicer, L,Citrome, L,Volavka, J(2017).Measurement of agitation and aggression in adult and aged neuropsychiatric patients: Review of definitions and frequently used measurement scales.CNS Spectr,22,407-414.
41. Volicer, L,Frijters, DH,Van der Steen, JT(2011).Underdiagnosis and undertreatment of depression in nursing home residents.Eur Geriat Med,2,332-337.
42. Volicer, L,Galik, E(2018).Agitation and aggression are 2 different syndromes in persons with dementia.J Am Med Dir Assoc,19,1035-1038.
43. Volicer, L,Pope, TM,Steinberg, KE(2019).Assistance with eating and drinking only when requested can prevent living with advanced dementia.J Am Med Dir Assoc,20,1353-1355.
44. Volicer, L,Stets, K(2016).Acceptability of an advance directive that limits food and liquids in advanced dementia.Am J Hosp Palliat Care,33,55-63.
45. Wang, J,Zhao, C,ZhaoA,Li, M,Ren, J,Qu, X(2015).New insights in amyloid beta interactions with human telomerase.J Am Chem Soc,137,1213-1219.
46. Xu, W,Tan, L,Wang, HF,Tan, MS,Tan, L,Li, JQ(2016).Education and risk of dementia: Dose-response meta-analysis of prospective cohort studies.Mol Neurobiol,53,3113-2123.
47. Zhan, XQ,Yao, JJ,Liu, DD,Ma, Q,Mei, YA(2013).Aß40 modulates GABAA receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway.J Neurochem,128,350-362.
48. Zhao, LN,Long, G,Mu, Y,Chew, LY(2012).The toxicity of amyloid ß oligomers.Int J Mol Sci,13,7303-7327.
49. Zou, K,Gong, JS,Yanagisawa, K,Michikawa, M(2002).A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage.J Neurosci,22,4833-4841.