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Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
Driscoll, Ira; Ma, Yue; Gallagher, Catherine L; Johnson, Sterling C; Asthana, Sanjay; Hermann, Bruce P; Sager, Mark A; Blennow, Kaj; Zetterberg, Henrik; Carlsson, Cynthia M; Engelman, Corinne D; Dubal, Dena B; Okonkwo, Ozioma C.
Afiliación
  • Driscoll I; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Ma Y; Wisconsin Alzheimer's Institute, Madison, WI, USA.
  • Gallagher CL; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
  • Johnson SC; Wisconsin Alzheimer's Institute, Madison, WI, USA.
  • Asthana S; Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, WI, USA.
  • Hermann BP; Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
  • Sager MA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Blennow K; Wisconsin Alzheimer's Institute, Madison, WI, USA.
  • Zetterberg H; Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, WI, USA.
  • Carlsson CM; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Engelman CD; Wisconsin Alzheimer's Institute, Madison, WI, USA.
  • Dubal DB; Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, WI, USA.
  • Okonkwo OC; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
J Alzheimers Dis ; 79(3): 1297-1305, 2021.
Article en En | MEDLINE | ID: mdl-33427737
BACKGROUND: Identification of new genetic variants that modify Alzheimer's disease (AD) risk will elucidate novel targets for curbing the disease progression or delaying symptom onset. OBJECTIVE: To examine whether the functionally advantageous KLOTHO gene KL-VS variant attenuates age-related alteration in cerebrospinal fluid (CSF) biomarkers or cognitive function in middle-aged and older adults enriched for AD risk. METHODS: Sample included non-demented adults (N = 225, mean age = 63±8, 68% women) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center who were genotyped for KL-VS, underwent CSF sampling and had neuropsychological testing data available proximal to CSF draw. Covariate-adjusted multivariate regression examined relationships between age group (Younger versus Older; mean split at 63 years), AD biomarkers, and neuropsychological performance tapping memory and executive function, and whether these relationships differed between KL-VS non-carriers (KL-VSNC) and heterozygote (KL-VSHET). RESULTS: In the pooled analyses, older age was associated with higher levels of total tau (tTau), phosphorylated tau (pTau), and their respective ratios to amyloid-ß (Aß)42 (ps ≤ 0.002), and with poorer performance on neuropsychological tests (ps ≤ 0.001). In the stratified analyses, KL-VSNC exhibited this age-related pattern of associations with CSF biomarkers (all ps ≤ 0.001), and memory and executive function (ps ≤ 0.003), which were attenuated in KL-VSHET (ps ≥ 0.14). CONCLUSION: Worse memory and executive function, and higher tau burden with age were attenuated in carriers of a functionally advantageous KLOTHO variant. KL-VS heterozygosity seems to be protective against age-related cognitive and biomolecular alterations that confer risk for AD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Disfunción Cognitiva / Glucuronidasa Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Disfunción Cognitiva / Glucuronidasa Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos