#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Is the role of amyloid in senile dementia substantial?


Authors: P. Kalvach 1;  K. Kupka 2;  M. Vogner 1
Authors‘ workplace: Neurologická klinika 3. LF UK a FN Královské Vinohrady, Praha 1;  Ústav nukleární medicíny, 1. LF UK a VFN v Praze 2
Published in: Cesk Slov Neurol N 2018; 81(2): 164-170
Category: Review Article
doi: https://doi.org/10.14735/amcsnn2018csnn.eu1

Overview

Extensive literature from the past 40 years accuses brain amyloid as one of the causal factors of senile dementia. Amyloid is considered, together with intracellular inclusions of τ-protein, as the originator for a specific Alzheimer‘s disease. After being dependent for many decades on amyloid detection only in autopsy specimens, the application of radioactive ligands using positron emission tomography (PET) currently achieves highly informative in vivo findings. The recognition of relations between mental acuity and the intensity of amyloid deposits has thus obtained a new dimension. We are providing a review of methods and their conclusions which shed light onto the mechanisms of brain ageing: histological properties of amyloid, techniques and the yield of its detection in PET, relation of amyloid density to that of neurofibrillary tangles, its relation to tissue metabolism and atrophy, dynamics of amyloid presence according to age and correlative studies between amyloid and mental effectivity. The given interpretation puts doubt on the causal role of amyloid in the psychic deterioration of seniors and thus also on one of the pillars of the so-called Alzheimer‘s disease.

Key words:
brain amyloid – Alzheimer‘s disease – dementia – senile atrophy – neurofibrillary tangles – hypometabolism – brain ageing – PET in dementia

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


Sources

1. Goedert M. Oskar Fischer and the study of dementia. Brain 2009; 132(4): 1002–1011. doi: 10.1093/brain/awn256.

2. Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift Psychiat Psychisch-Gerichtlich Med 1907; 64: 146–148.

3. Fischer O. Miliäre Nekrosen mit drusigen Wucherungen der Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei seniler Demenz. Mschr Psychiat Neurol 1907; 22: 361–372. doi:10.1159/000211873.

4. Fischer O. Die presbyophrene Demenz, deren anatomische Grundlage und klinische Abgrenzung. Zeitschr Ges Neurol Psychiatr 1910; 3(1): 371–471.

5. Kalvach P, Kalvach Z. History of dementia research in Bohemia and middle Europe. Neurodegener Dis 2010; 7(1–3): 6–9. doi: 10.1159/000283474.

6. Peng F. Alzheimer‘s disease: what is it after all? Taipei: Ho-Chi Book Publishing Company 2012.

7. Braun B, Stadlober-Degwerth M, Klünemann HH. La malattia di Alzheimer-Perusini. Zum 100. Jahrestag der Publikation Gaetano Perusinis. Nervenarzt 2011; 82(3): 363–369. doi: 10.1007/s00115-010-2984-x.

8. Sipe JD, Cohen AS. Review: history of the amyloid fibril. J Struct Biol 2000; 130: 88–98.

9. Hardy JA, Higgins GA. Alzheimer‘s disease: the amyloid cascade hypothesis. Science 1992; 256(5054): 184–185.

10. Price JL, Morris JC. Tangles and plaques in nondemented aging and „preclinical“ Alzheimer´s disease. Ann Neurol 1999; 45(3): 358–368.

11. Morris GP, Clark IA, Vissel B. Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer‘s disease. Acta Neuropathol Commun 2014; 2: 135. doi: 10.1186/s40478-014-0135-5.

12. Klunk WE, Engler H, Nordberg A et al. Imaging brain amyloid in Alzheimer‘s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55(3): 306–319.

13. Seibyl J, Stephens A, Barthel H et al. A negative florbetaben PET scan reliably excludes amyloid pathol­ogy – a histopathology confirmation multi-centre study. Eur J Nucl Med Mol Imaging 2014; 41 (Suppl 2): S259.

14. Fodero-Tavoletti MT, Rowe ChC, McLean CA et al. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med 2009; 50(2): 198–204. doi: 10.2967/jnumed.108.057984.

15. Kepe V, Moghbel MC, Långström B et al. Amyloid beta- positron emission tomography imaging probes: a critical review. J Alzheimers Dis 2013; 36(4): 613–631. doi: 10.3233/JAD-130485.

16. Stankoff B, Freeman L, Aigrot MS et al. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4´-methylaminophenyl)-6-hydroxybenzylthiazole. Ann Neurol 2011; 69(4): 673–680. doi: 10.1002/ana.22320.

17. Glodzik L, Rusinek H, Li J et al. Reduced retention of Pittsburg compound B in white matter lesions. Eur J Nucl Med Mol Imaging 2015; 42(1): 97–102. doi: 10.1007/s00259-014-2897-1.

18. Frey KA. Amyloid imaging in dementia: contribution or confusion? J Nucl Med 2015; 56(3): 331–332. doi: 10.2967/jnumed.114.151571.

19. Westerman M, Cooper-Blacketer D, Mariash A et al. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer‘s disease. J Neurosci 2002; 22(5): 1858–1867.

20. Neuropathology Group. Medical research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre community-based population in England and Wales. Lancet 2001; 357(9251): 169–175.

21. Love S, Louis D, Ellison DW et al. Greenfield‘s Neuropathology. 8th ed. London: CRC Press. 2008.

22. Geschwind MD. Rapidly progessive dementia. Continuum (Minneap Minn) 2016; 22 (2 Dementia): 510–537. doi: 10.1212/CON.0000000000000319.

23. Rowe CC, Ellis KA, Rimajova M et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 2010; 31(8): 1275–1283. doi: 10.1016/j.neurobiolaging.2010.04.007.

24. Jagust WJ, Landau SM, Shaw LM et al. Relationships between biomarkers in aging and dementia. Neurology 2009; 73(15): 1193–1199. doi: 10.1212/WNL.0b013e3181bc010c.

25. Lowe WJ, Kemp BJ, Jack CR Jr et al. Comparison of 18F-FDG and PIB PET in cognitive impairment. J Nucl Med 2009; 50(6): 878–886. doi: 10.2967/jnumed.108.058529.

26. Jack CR Jr, Lowe WJ, Senjem ML et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer‘s disease and amnestic mild cog­nitive impairment. Brain 2008; 131(3): 665–680. doi: 10.1093/brain/awm336.

27. Mormino EC, Brandel MG, Madison CM et al. Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. Neuroimage 2012; 59(2): 1152–1160. doi: 10.1016/j.neuroimage.2011.07.098.

28. Fleischer AS, Chen K, Liu X et al. Using positron emis­sion tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol 2011; 68(11): 1404–1411. doi: 10.1001/archneurol.2011.150.

29. Rodrigue KM, Kennedy KM, Devous MD Sr et al. β-amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology 2012; 78(6): 387–395. doi: 10.1212/WNL.0b013e318245d295.

30. Sperling RA, Johnson KA, Doraiswamy PM et al. Amyloid deposition detected with florbetapir F18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging 2013; 34(3): 822–831. doi: 10.1016/j.neurobiolaging.2012.06.014.

31. Katzman R. Alzheimer´s disease as an age-dependent disorder. In: Research and the ageing population. CIBA Foundation Symposium 134. Chichester: John Wiley and sons 1988: 69–85. Available from URL: http://onlinelibrary.wiley.com/doi/10.1002/9780470513583.fmatter/pdf.

32. Price DL, Walker LC, Martin LJ et al. Amyloidosis in aging and Alzheimer´s disease. Am J Pathol 1992; 141(4): 762–772.

33. Doraiswamy PM, Sperling RA, Coleman RE et al. Amyloid-β assessed by florbetapir F18 PET and 18 months cognitive decline: a multicenter study. Neurology 2012; 79(16): 1636–1644. doi: 10.1212/WNL.0b013e3182661f74.

34. Chételat G, La Joie R, Villain N et al. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer´s disease. Neuroimage Clin 2013; 2: 356–365. doi: 10.1016/j.nicl.2013.02.006.

35. Chételat G. Alzheimer disease: Aβ-independent processes-rethinking preclinical AD. Nat Rev Neurol 2013; 9(3): 123–124. doi: 10.1038/nrneurol.2013.21.

36. Savva GM, Wharton SB, Ince PG et al. Age, neuropathology and dementia. N Engl J Med 2009; 360(22): 2302–2309. doi: 10.1056/NEJMoa0806142.

37. Duyckaerts C, Dickson D. Neuropathology of Alzheimer‘s disease and its variants. In: Neurodegeneration: The molecular pathology of dementia and movement disorders. Oxford: Wiley-Blackwell 2011: 477.

38. Price JL, Morris JC. Tangles and plaques in nondemented aging and „preclinical“ Alzheimer‘s disease. Ann Neurol 1999; 45(3): 358–368.

39. Braak H, Thal DR, Ghebremedhin E et al. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011; 70(11): 960–969. doi: 10.1097/NEN.0b013e318232a379.

40. Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol 2009; 68(1): 1–14. doi: 10.1097/NEN.0b013e3181919a48.

41. Korczyn AD. The amyloid cascade hypothesis. Alzheimers Dement 2008; 4(3): 176–178. doi: 10.1016/j.jalz.2007.11.008.

42. He W, Liu D, Radua J et al. Meta-analytic comparison between PIB-PET and FDG-PET results in Alzheimer‘s dis­ease and MCI. Cell Biochem Biophys 2015; 71(1): 17–26. doi: 10.1007/s12013-014-0138-7.

43. Knopman DS, Jack CR Jr, Wiste HJ et al. Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Ann Neurol 2013; 73(4): 472–480. doi: 10.1002/ana.23816.

44. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer‘s disease at 25 years. EMBO Mol Med 2016; 8(6): 595–608. doi: 10.15252/emmm.201606210.

45. de la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002; 33(4): 1152–1162.

46. Iadecola C. The pathobiology of vascular dementia. Neuron 2013; 80(4): 844–866. doi: 10.1016/j.neuron.2013.10.008.

47. Xiong YY, Mok V. Age-related white matter changes. J Aging Res 2011; 2011: 617927. doi: 10.4061/2011/617927.

48. Schmidt R, Petrovic K, Ropele S et al. Progression of leukoaraiosis and cognition. Stroke 2007; 38(9): 2619–2625.

49. Brundel M, de Bresser J, van Dillen JJ et al. Cerebral microinfarcts: a systematic review of neuropathological studies. J Cereb Blood Flow Metab 2012; 32(3): 425–436. doi: 10.1038/jcbfm.2011.200.

50. Van Rooden S, Goos JDC, van Opstal AM et al. Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging. Radiology 2014; 270(1): 205–211. doi: 10.1148/radiol.13130743.

51. Kalaria RN, Kenny RA, Ballard CG et al. Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 2004; 226(1–2): 75–80.

52. McAleese KE, Alafuzoff I, Charidimou A et al. Post-mortem assessment in vascular dementia: advances and aspirations. BMC Med 2016; 14(1): 129–140. doi.10.1186/s12916-016-0676-5.

53. Yates PA, Villemagne VL, Ellis KA et al. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol 2013; 4: 205–218. doi: 10.3389/fneur.2013.00205.

54. Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited. Recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83(2): 124–137. doi: 10.1136/jnnp-2011-301308.

55. Giorgio A, Santelli L, Tomassini V et al. Age-relat­ed changes in gray and white matter structure throughout adulthood. Neuroimage 2010; 51(3): 943–951. doi: 10.1016/j.neuroimage.2010.03.004.

56. Sexton CE, Walhovd KB, Storsve AB et al. Accelerat­ed changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study. J Neurosci 2014; 34(46): 15425–15436. doi: 10.1523/JNEUROSCI.0203-14.2014.

57. Reisberg B, Franssen EH, Hasan SM et al. Retrogenesis: clinical, physiologic and pathologic mechanisms in brain aging, Alzheimer‘s and other dementing proces­ses. Eur Arch Psychiatry Clin Neurosci 1999; 249 (Suppl 3):28–36.

58. Rohan Z, Matěj R, Rusina R. Překrývání neurodegenerativních demencí. Cesk Slov Neurol N 2015; 78/111(6): 641–648. doi: 10.14735/amcsnn2015641.

Labels
Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 2

2018 Issue 2

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#