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01.11.2012 | Original Paper

Neuropathologically defined subtypes of Alzheimer’s disease differ significantly from neurofibrillary tangle-predominant dementia

verfasst von: Nicholas J. Janocko, Kevin A. Brodersen, Alexandra I. Soto-Ortolaza, Owen A. Ross, Amanda M. Liesinger, Ranjan Duara, Neill R. Graff-Radford, Dennis W. Dickson, Melissa E. Murray

Erschienen in: Acta Neuropathologica | Ausgabe 5/2012

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Abstract

Alzheimer’s disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18) with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.

Alladi S, Xuereb J, Bak T et al (2007) Focal cortical presentations of Alzheimer’s disease. Brain 130:2636–2645PubMedCrossRef

Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445PubMedCrossRef

Bancher C, Egensperger R, Kosel S, Jellinger K, Graeber MB (1997) Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol 94:403–409PubMedCrossRef

Barker WW, Luis CA, Kashuba A et al (2002) Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord 16:203–212PubMedCrossRef

Braak H, Braak E (1990) Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia. Acta Neuropathol 80:479–486PubMedCrossRef

Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259PubMedCrossRef

Cairns N, Bigio E, Mackenzie I et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114:5–22PubMedCrossRef

Dugger BN, Tu M, Murray ME, Dickson DW (2011) Disease specificity and pathologic progression of tau pathology in brainstem nuclei of Alzheimer’s disease and progressive supranuclear palsy. Neurosci Lett 491:122–126PubMedCrossRef

Duyckaerts C, Delatour B, Potier M-C (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118:5–36PubMedCrossRef

10.

Espinoza M, de Silva R, Dickson DW, Davies P (2008) Differential incorporation of tau isoforms in Alzheimer’s disease. J Alzheimers Dis 14:1–16PubMed

11.

Folstein MF, Folstein SE, McHugh PR (1975) “Mini-Mental State”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRef

12.

Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123(Pt 3):484–498PubMedCrossRef

13.

Hasegawa M, Arai T, Akiyama H et al (2007) TDP-43 is deposited in the Guam parkinsonism–dementia complex brains. Brain 130:1386–1394PubMedCrossRef

14.

Hatanpaa KJ, Bigio EH, Cairns NJ et al (2008) TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a Midwest-Southwest Consortium for FTLD study. J Neuropathol Exp Neurol 67:271–279PubMedCrossRef

15.

Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097PubMedCrossRef

16.

Hyman BT, West HL, Rebeck GW et al (1995) Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proc Natl Acad Sci USA 92:3586–3590PubMedCrossRef

17.

Ikeda K, Akiyama H, Arai T et al (1999) Clinical aspects of ‘senile dementia of the tangle type’— a subset of dementia in the senium separable from late-onset Alzheimer’s disease. Dement Geriatr Cogn Disord 10:6–11PubMedCrossRef

18.

Ikeda K, Akiyama H, Arai T et al (1997) A subset of senile dementia with high incidence of the apolipoprotein E epsilon2 allele. Ann Neurol 41:693–695PubMedCrossRef

19.

Iseki E, Yamamoto R, Murayama N et al (2006) Immunohistochemical investigation of neurofibrillary tangles and their tau isoforms in brains of limbic neurofibrillary tangle dementia. Neurosci Lett 405:29–33PubMedCrossRef

20.

Jellinger KA (2012) Neuropathological subtypes of Alzheimer’s disease. Acta Neuropathol 123:153–154PubMedCrossRef

21.

Jellinger KA, Attems J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113:107–117PubMedCrossRef

22.

Jellinger KA, Bancher C (1998) Senile dementia with tangles (tangle predominant form of senile dementia). Brain Pathol 8:367–376PubMedCrossRef

23.

Josephs KA, Whitwell JL, Knopman DS et al (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857PubMedCrossRef

24.

Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097–1105PubMedCrossRef

25.

Kim J, Miller VM, Levites Y et al (2008) BRI2 (ITM2b) inhibits Abeta deposition in vivo. J Neurosci 28:6030–6036PubMedCrossRef

26.

Knopman DS, Jack CR, Wiste HJ et al (2012) Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology 78:1576–1582PubMedCrossRef

27.

Koivunen J, Verkkoniemi A, Aalto S et al (2008) PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer’s disease. Brain 131:1845–1853PubMedCrossRef

28.

Murray ME, Dickson DW (2008) O1-01-02: Alzheimer’s disease with relative hippocampal sparing: a distinct clinicopathologic variant. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 4:T106–1106

29.

Murray ME, Graff-Radford NR, Ross OA et al (2012) Differentiating clinicopathologic and genetic aspects of hippocampal sclerosis in Alzheimer’s disease from limbic predominant Alzheimer’s disease and “pure” hippocampal sclerosis. Alzheimer’s Dementia J Alzheimer’s Assoc 8:P620–P621

30.

Murray ME, Graff-Radford NR, Ross OA et al (2011) Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 10:785–796PubMedCrossRef

31.

Nelson PT, Abner EL, Schmitt FA et al (2009) Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol 68:774–784PubMedCrossRef

32.

Nitrini R, Lopes K, Brucki SMD (2011) Previous description of subtypes of Alzheimer’s pathology. Dement Neuropsychol 5:346–348

33.

Noda K, Sasaki K, Fujimi K et al (2006) Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle-only dementia): the Hisayama Study. Neuropathology 26:508–518PubMedCrossRef

34.

Santa-Maria I, Haggiagi A, Liu X et al (2012) The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol. doi:10.1007/s00401-012-1017-1

35.

Schmechel DE, Saunders AM, Strittmatter WJ et al (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 90:9649–9653PubMedCrossRef

36.

Terry RD, Hansen LA, DeTeresa R et al (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol 46:262–268PubMedCrossRef

37.

Togo T, Sahara N, Yen SH et al (2002) Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol 61:547–556PubMed

38.

Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697PubMedCrossRef

39.

van der Flier WM, Pijnenburg YAL, Fox NC, Scheltens P (2011) Early-onset versus late-onset Alzheimer’s disease: the case of the missing APOE [var epsilon]4 allele. Lancet Neurology 10:280–288PubMedCrossRef

40.

van Duijn CM, de Knijff P, Cruts M et al (1994) Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer’s disease. Nat Genet 7:74–78PubMedCrossRef

41.

Whitwell JL, Jack CR, Jr., Przybelski SA et al (2009) Temporoparietal atrophy: a marker of AD pathology independent of clinical diagnosis. Neurobiol Aging 32:1531–1541

42.

Yen SH, Dickson DW, Crowe A, Butler M, Shelanski ML (1987) Alzheimer’s neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2. Am J Pathol 126:81–91PubMed

43.

Yokota O, Davidson Y, Bigio EH et al (2010) Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy. Acta Neuropathol 120:55–66PubMedCrossRef

44.

Yokota O, Terada S, Ishizu H et al (2002) NACP/alpha-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC). Acta Neuropathol 104:333–341PubMed

Titel: Neuropathologically defined subtypes of Alzheimer’s disease differ significantly from neurofibrillary tangle-predominant dementia
verfasst von: Nicholas J. Janocko
Kevin A. Brodersen
Alexandra I. Soto-Ortolaza
Owen A. Ross
Amanda M. Liesinger
Ranjan Duara
Neill R. Graff-Radford
Dennis W. Dickson
Melissa E. Murray
Publikationsdatum: 01.11.2012
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 5/2012
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-012-1044-y

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