Concomitant LATE-NC in Alzheimer's disease is not associated with increased tau or amyloid-ß pathological burden.
Neuropathol Appl Neurobiol
; 46(7): 722-734, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32896913
ABSTRACT
AIMS:
Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is present in approximately 50% of Alzheimer's disease (AD) cases and is associated with accelerated cognitive decline. Studies indicate a potential synergistic relationship between LATE-NC and hyperphosphorylated tau. It is unknown if LATE-NC is an independent driver of cognitive impairment or exerts its influence through synergistic relationships with tau. This cliniconeuropathological study investigated the impact of LATE-NC on quantified measures of AD-associated pathology and its impact on clinical measures.METHODS:
A total of 61 AD cases underwent neuropathological assessment for LATE-NC and quantitative assessment [area covered by immunoreactivity (IR)] for early conformational tau (MC-1), late-stage hyperphosphorylated tau (AT8) and amyloid-ß in the amygdala and five neocortical regions. Clinical measures included age of disease onset, final Mini-Mental State Examination (MMSE) score and rate of cognitive decline.RESULTS:
LATE-NC was present in 41 AD cases (AD/LATE-NC; 67.2%). No significant differences in MC-1-IR, AT8-IR or 4G8-IR were observed in any region between AD/LATE-NC and AD without LATE-NC, indicating no accelerated aggregation or hyperphosphorylation of tau proteins in the AD/LATE-NC cases. Final MMSE was significantly lower in AD/LATE-NC cases and was significantly associated with LATE-NC score even when controlled for the presence of both MC-1-IR and AT8-IR (P = 0.009).CONCLUSION:
The presence of LATE-NC in AD is not associated with an increase in the burden of early or late tau or Aß pathology. LATE-NC is associated with a lower final MMSE score independent of tau pathology.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Proteínas tau
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Proteínas de Ligação a DNA
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Doença de Alzheimer
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido