Spreading of amyloid, tau, and microvascular pathology in alzheimer's disease: Findings from neuropathological and neuroimaging studies

Journal of Alzheimer's Disease

Volumn 42, Issue , 2014, Pages S421-S429

  Thal, Dietmar Rudolf ^a   Attems, Johannes ^b   Ewers, Michael ^c  

^a UNIVERSITY OF ULM   (Germany)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Alzheimer's disease; amyloid ; biomarker; diagnosis; early detection; magnetic resonance imaging; neurofibrillary tangles; plaques; positron emission tomography; small vessel disease

Indexed keywords

AMYLOID BETA PROTEIN; BIOLOGICAL MARKER; FLUORINE 18; TAU PROTEIN; TRACER; AMYLOID;

ALLOCORTEX; ALZHEIMER DISEASE; AMYLOID PLAQUE; ARTERIOLOSCLEROSIS; ATHEROSCLEROSIS; BASAL GANGLION; BRAIN REGION; COGNITION; CORTICOBASAL DEGENERATION; DEMENTIA; DISEASE COURSE; EPISODIC MEMORY; EXECUTIVE FUNCTION; HUMAN; LOCUS CERULEUS; MICROANGIOPATHY; NEOCORTEX; NEUROFIBRILLARY TANGLE; NEUROIMAGING; NEUROPATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PICK PRESENILE DEMENTIA; POSITRON EMISSION TOMOGRAPHY; PREDICTIVE VALUE; PROGRESSIVE SUPRANUCLEAR PALSY; PYRAMIDAL NERVE CELL; RAPHE NUCLEUS; REVIEW; SENILE PLAQUE; VASCULAR AMYLOIDOSIS; VASCULAR DISEASE; WHITE MATTER HYPERINTENSITIES; WHITE MATTER LESION; METABOLISM; MICROVASCULATURE; PATHOLOGY;

ALZHEIMER DISEASE; AMYLOID; HUMANS; MICROVESSELS; NEUROIMAGING; TAU PROTEINS;

EID: 84908222292     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-141461     Document Type: Review

References (63)

1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr., Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of A lzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 280-292.
2. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mil d cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 270-279.
3. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge R, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M, nEuroimaging STfRVco (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12, 822-838.
4. Gold G, Giannakopoulos P, Herrmann FR, Bouras C,Kovari E (2007) Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130, 2830-2836.
5. Bell RD, Z lokovic BV (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol 118, 103-113.
6. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ (2012) National Institute on Aging-Alzheimer's As sociation guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 8, 1-13.
7. Alzheimer A (1907) Ueber eine eigenartige Erkrankung der Hirnrinde. Allg Zschr Psych 64, 146-148.
8. Price JL, Davis PB, Morris JC, White DL (1991) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol Aging 12, 295-312.
9. Rijal Upadhaya A, Kosterin I, Kumar S, Von Arnim C, Yamaguchi H, Fändrich M,Walter J, Thal DR (2014) Biochemical stages of amyloid-peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically-preclinical Alzheimer's disease. Brain 137, 887-903.
10. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82, 4245-4249.
11. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56, 321-339.
12. Thal DR, Capetillo-Zarate E, Del Tredici K, Braak H (2006) The development of amyloid beta protein deposits in the aged brain. Sci Aging Knowledge Environ 2006, re1.
13. Griffin WS, Sheng JG, Roberts GW, Mrak RE (1995) Interleukin-1 expression in different plaque types in Alzheimer's disease: Significance in plaque evolution. J Neuropathol Exp Neurol 54, 276-2 81.
14. Thal DR, Rub U, Schultz C, Sassin I, Ghebremedhin E, Del Tredici K, Braak E, Braak H (2000) Sequence of Abetaprotein deposition in the human medial temporal lobe. J Neuropathol Exp N eurol 59, 733-748.
15. WisniewskiHM,Sadowski M, Jakubowska-Sadowska K,Tarnawski M, Wegiel J (1998) Diffuse, lake-like amyloid-beta deposits in the parvopyramidal layer of the presubiculum in Alzheimer di sease. J Neuropathol Exp Neurol 57, 674-683.
16. Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of Abeta-deposition in the human brain and its relevance for the development of AD. Neurology 58, 1791-1800.
17. Braak E, Braak H, Mandelkow EM (19 94) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87, 554-567.
18. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, W isniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-Associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83, 4913-4917.
19. Bancher C, Br unner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477, 90-99.
20. Braak H, Braak E (1988) Neuropil threads occur in dendrites of tangle-bearing nerve cells. Neuropathol Appl Neurobiol 14, 39-44.
21. Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen SH (1988) Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am J Pathol 132, 86-101.
22. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82, 239-259.
23. Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J Neuropathol Exp Neurol 70, 960-969.
24. Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol 121, 171-181.
25. Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathological process in Alzheimer's disease: Age categorie s 1 year to 100 years. J Neuropathol Exp Neurol 70, 960-969.
26. Thal DR, DelTredici K, BraakH(2004) Neurodegeneration in normal brain aging and disease. Sci Aging Knowledge Environ 2004, PE26.
27. Grinberg LT, Thal DR (2010) Vascular pathology in the aged human brain. Acta Neuropathol 119, 277-290.
28. Luoto TM, Haikonen S, Haapasalo H, Goebeler S, Huhtala H, Erkinjuntti T, Karhunen PJ (2009) Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer's disease. Eur Neurol 62, 93-98.
29. Zheng L, Vin ters HV, Mack WJ, Zarow C, Ellis WG, Chui HC (2013) Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer pathologic changes. Stroke 44, 2835-2841.
30. Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, O'Brien RJ (2010) Atherosclerosis, dementia, and Alzheimer's disease in the BLSA cohort. Ann Neurol 68, 231-240.
31. Thal DR,Ghebremedhin E,Orantes M,Wiestler OD 2003 Vascular pathology in Alzheimer disease: Correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline J Neuropathol Exp Neurol 62, 1287-1301.
32. Young VG, Halliday GM, Kril JJ (2008) Neuropathologic correlates of white matter hyperintensities. Neurology 71, 804-811.
33. Polvikoski TM, van Straaten EC, Barkhof F, Sulkava R, Aronen HJ, Niinisto L, Oinas M, Scheltens P, Erkinjuntti T, Kalaria RN (2010) Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old. Neur ology 75, 2071-2078.
34. McAleese KE, Firbank M, Hunter D, Sun L, Hall R, Neal JW, MannDM,Esiri M, Jellinger KA, O'Brien JT, Attems J (2013) Magnetic resonance imaging of fixed pos t mortem brains reliably reflects subcortical vascular pathology of frontal, parietal and occipital white matter. Neuropathol Appl Neurobiol 39, 485-497.
35. Esiri MM, Joachim C, Sloan C, Christie S, Agacinski G, Bridges LR, Wilcock GK, Smith AD (2014) Cerebral subcortical small vessel disease in subjects with pathologically confirmed Alzheimer disease: A clinicopathologic study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). Alzheimer Dis Assoc Disord 28, 30-35.
36. Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O'Keefe G, Price R, Raniga P, Robins P, Acosta O, Lenzo N, Szoeke C, Salvado O, Head R, Martins R, Masters CL, Ames D, Villemagne VL (2010) Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31, 1275-1283.
37. Klunk WE (2011) Amyloid imaging as a biomarker for cerebral beta-Amyloidosis and risk prediction for Alzheimer dementia. Neurobiol Aging 32(Suppl 1), S20-S36.
38. Benzinger TL, Blazey T, Jack CR Jr.,Koeppe RA, SuY, Xiong C, Raichle ME, Snyder AZ, Ances BM, Bateman RJ, Cairns NJ, Fagan AM, Goate A, Marcus DS, Aisen PS, Christensen JJ, Ercole L, Hornbeck RC, Farrar AM, Aldea P, Jasielec MS, Owen CJ, Xie X, Mayeux R, Brickman A, McDade E, Klunk W, Mathis CA, Ringman J, Thompson PM, Ghetti B, Saykin AJ, Sperling RA, John s on KA, Salloway S, Correia S, Schofield PR, Masters CL, Rowe C, Villemagne VL, Martins R, Ourselin S, Rossor MN, Fox NC, Cash DM, Weiner MW, Holtzman DM, Buckles VD, Moulder K, Morris JC (201 3) Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease. Proc Natl Acad Sci U S A 110, E4502-E4509.
39. Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, Hiemeyer F, Wittemer-Rump SM, Seibyl J, Reininger C, Sabri O (2011) Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: A multicentre phase 2 diagnostic study. Lancet Neurol 10, 424-435.
40. Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58, 1791-1800.
41. Ikonomovic MD, Abrahamson EE, Price JC, Hamilton RL, Mathis CA, Paljug WR, Debnath ML, Cohen AD, Mizukami K, DeKosky ST, Lopez OL, Klunk WE (2012) Early AD pathology in a [C-11]PiB-negative case: A PiB-Amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol 123, 433-447.
42. Landau SM, Mintun MA, Joshi AD, Koeppe RA, Petersen R C, Aisen PS,WeinerMW, Jagust WJ (2012) Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol 72, 578-586.
43. Hedden T, Oh H, Younger AP, Patel TA (2013) Meta-Analysis of amyloid-cognition relations in cognitively normal older adults. Neurology 80, 1341-1348.
44. Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, Ackermann U, Jones G, Szoeke C, Salvado O, Martins R, O'Keefe G, Mathis CA, Klunk WE, Ames D, Masters CL, Rowe CC (2011) Longitudinal asse ssment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol 69, 181-192.
45. Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzma n DM, Fagan AM (2013) Preclinical Alzheimer's disease and its outcome: A longitudinal cohort study. Lancet Neurol 12, 957-965.
46. Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Co nnor AR, McLean CA, Cao D, Rigopoulos A, Cartwright GA, O'Keefe G, Gong S, Adlard PA, Barnham KJ, Rowe CC, Masters CL, Kudo Y, Cappai R, Yanai K, Villemagne VL (2011) 18F-THK523: A novel in vivo tau imaging ligand for Alzheimer's disease. Brain 134, 1089-1100.
47. Chien DT, Bahri S, Szardenings AK,Walsh JC, Mu F, SuMY, Shankle WR, Elizarov A, Kolb HC (2013) Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis 34, 457-468.
48. Chien DT, Szardenings AK, Bahri S,Walsh JC, Mu F, Xia C, Shankle WR, Lerner AJ , SuMY, Elizarov A, Kolb HC (2014) Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis 38, 171-184.
49. Maruyama M, Shimada H, Suh ara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski JQ, Lee VM, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, KudoY, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, HiguchiM(2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79, 1094-1108.
50. Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC (2012) A hig hly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis 31, 601-612.
51. Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, Pejoska S, Kudo Y, Masters CL, Yanai K, Rowe CC, Villemagne VL (2014) Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18FTHK5105 PET. Brain 137(Pt 6), 1762-1771.
52. Lee VM,Goedert M,Trojanowski JQ 2001) Neurodegenerative tauopathies Annu Rev Neurosci 24, 1121-1159.
53. Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, Kalaria RN (2 012) Staging and natural history of cerebrovascular pathology in dementia. Neurology 78, 1043-1050.
54. Duering M, Zieren N, Herve D, Jouvent E, Reyes S, Peters N, Pachai C, Opherk C , Chabriat H, Dichgans M (2011) Strategic role of frontal white matter tracts in vascular cognitive impairment: A voxel-based lesion-symptom mapping study in CADASIL. Brain 134, 2366-2375.
55. DueringM,Gesierich B, Seiler S, Pirpamer L, GonikM,Hofer E, Jouvent E, Duchesnay E, Chabriat H, Ropele S, Schmidt R, Dichgans M (2014) Strategic white matter tracts for processing speed deficits in age-related small vessel disease. Neurology 82, 1946-1950.
56. Lo RY, Jagust WJ, Alzheimer's Disease Neuroimaging I (2012) Vascular burden and Alzheimer disease pathologic progression. Neurology 79, 1349-1355.
57. Noh Y, Seo SW, Jeon S, Lee JM, Kim JH, Kim GH, Cho H, Yoon CW, Kim HJ, Ye BS, Kim ST, Choe YS, Lee KH, Kim JS, Ewers M, Weiner MW, Lee JH, Werr ing DJ, Kang DR, Kim CS, Na DL (2014) White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers. J Alzheimers Dis 40, 877-886.
58. Debette S, Markus HS (2010) T he clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-Analysis. BMJ 341, c3666.
59. Park JH, Seo SW, Kim C, Kim SH, Kim GH, Kim S T, Jeon S, Lee JM, Oh SJ, Kim JS, Choe YS, Lee KH, Shin JS, Kim CH, Noh Y, Cho H, Yoon CW, Kim HJ, Ye BS, Ewers M, Weiner MW, Lee JH, Werring DJ, Na DL (2014) Effects of cerebrov ascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment. Neurobiol Aging 35, 254-260.
60. Smith EE, Salat DH, Jeng J, McCreary CR, Fischl B, Schmahmann JD, Dickerson BC, Viswanathan A, Albert MS, Blacker D, Greenberg SM (2011) Correlations between MRI white matter lesion location and executive function and episodic memory. Neurology 76, 1492-1499.
61. Jacobs HI, Visser PJ, Van Boxtel MP, Frisoni GB, Tsolaki M, Papapostolou P, Nobili F, Wahlund LO, Minthon L, Frolich L, Hampel H, Soininen H, van de Pol L, Scheltens P, Tan FE, Jolles J, Verhey FR (2012) Association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent. Neurobiol Aging 33, 201 e201-e208.
62. Chao LL, Deca rli C, Kriger S, Truran D, Zhang Y, Laxamana J, Villeneuve S, Jagust WJ, Sanossian N, Mack WJ, Chui HC, Weiner MW (2013) Associations between white matter hyperintensities and beta amyloid on integrity of proje ction, association, and limbic fiber tracts measured with diffusion tensor MRI. PLoS One 8, e65175.
63. Thal DR, Grinberg LT, Attems J (2012) Vascular dementia: Different forms of vessel disorders contri bute to the development of dementia in the elderly brain. Exp Gerontol 47, 816-824.