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10.1186/s40478-019-0687-5

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suck abstract from ncbi


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pmid30832741      Acta+Neuropathol+Commun 2019 ; 7 (1): 34
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  • Detection of Alzheimer s disease (AD) specific tau pathology with conformation-selective anti-tau monoclonal antibody in co-morbid frontotemporal lobar degeneration-tau (FTLD-tau) #MMPMID30832741
  • Gibbons GS; Kim SJ; Robinson JL; Changolkar L; Irwin DJ; Shaw LM; Lee VM; Trojanowski JQ
  • Acta Neuropathol Commun 2019[Mar]; 7 (1): 34 PMID30832741show ga
  • Pathological tau aggregates in Alzheimer's disease (AD) and frontotemporal lobar degeneration-tau (FTLD-tau) adopt distinct conformations differentiated by the AD-tau specific monoclonal antibody (mAb) GT-38 that are not readily visualized using phosphorylation-specific anti-tau mAbs. To determine the extent of co-morbid AD-tau pathology in FTLD-tau, we performed immunohistochemical (IHC) staining with GT-38 and assigned Braak stages of AD-tau in a cohort 180 FTLD-tau cases consisting of corticobasal degeneration (CBD; n = 49), progressive supranuclear palsy (PSP; n = 109), and Pick's disease (PiD; n = 22). Nearly two-thirds of patients (n = 115 of 180, 63.8%) with FTLD-tau had some degree of comorbid AD-tau pathology and 20.5% of the FTLD-tau cohort had Braak stage >/=B2, consistent with medium-to-high-level AD neuropathological change (ADNPC). The PSP group had the highest frequency of medium-high AD-tau pathology compared to other tauopathies (PSP = 31/109, 28.4%; Picks = 2/22, 9.1%, CBD = 4/49, 8.2%) but neuropathological diagnosis was not found to be a significant independent predictor of medium-high AD Braak stage in a multivariate model after accounting for age at death (OR = 1.09; 95% CI = 1.03-1.15; p = 0.002) and CERAD plaque scores (OR = 3.75, 95% CI = 1.58-8.89; p = 0.003), suggesting there is no predilection for a specific FTLD tauopathy to develop AD-tau co-pathology after accounting for age. Patients with FTLD-tau who had, clinically significant, medium-high AD-tau pathology had significantly higher antemortem CSF levels of both total-tau (t-tau; mean = 89.98 pg/ml, SD = 36.70 pg/ml) and phosphorylated-tau (p-tau; mean = 20.45 pg/ml, SD = 9.31 pg/ml) compared to patients with negligible-low AD-tau, t-tau (mean = 43.04 pg/ml, SD = 25.40 pg/ml) and p-tau (mean = 11.90 pg/ml, SD = 4.48 pg/ml) (p
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Alzheimer Disease/genetics/*metabolism/pathology[MESH]
  • |Antibodies, Monoclonal/chemistry/*metabolism[MESH]
  • |Comorbidity[MESH]
  • |Female[MESH]
  • |Frontotemporal Lobar Degeneration/genetics/*metabolism/pathology[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Protein Conformation[MESH]
  • |Tauopathies/genetics/*metabolism/pathology[MESH]


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