Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

<h4>Objective</h4>A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.<h4>Design</h4>Cross-sectional analyses of data...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Erika J Lampert, Kingshuk Roy Choudhury, Christopher A Hostage, Jeffrey R Petrella, P Murali Doraiswamy, Alzheimer’s Disease Neuroimaging Initiative
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f00228b9b6e04b159ff04337c0d55f52
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f00228b9b6e04b159ff04337c0d55f52
record_format	dspace
spelling	oai:doaj.org-article:f00228b9b6e04b159ff04337c0d55f522021-11-18T07:49:09ZPrevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.1932-620310.1371/journal.pone.0060747https://doaj.org/article/f00228b9b6e04b159ff04337c0d55f522013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23613741/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.<h4>Design</h4>Cross-sectional analyses of data from a national biomarker study.<h4>Setting</h4>The Alzheimer's Disease Neuroimaging Initiative national study.<h4>Patients</h4>257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.<h4>Outcome measures</h4>Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.<h4>Statistics</h4>Univariate and multivariate analyses.<h4>Results</h4>In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group.<h4>Conclusions</h4>A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.Erika J LampertKingshuk Roy ChoudhuryChristopher A HostageJeffrey R PetrellaP Murali DoraiswamyAlzheimer’s Disease Neuroimaging InitiativePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60747 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erika J Lampert Kingshuk Roy Choudhury Christopher A Hostage Jeffrey R Petrella P Murali Doraiswamy Alzheimer’s Disease Neuroimaging Initiative Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
description	<h4>Objective</h4>A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.<h4>Design</h4>Cross-sectional analyses of data from a national biomarker study.<h4>Setting</h4>The Alzheimer's Disease Neuroimaging Initiative national study.<h4>Patients</h4>257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.<h4>Outcome measures</h4>Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.<h4>Statistics</h4>Univariate and multivariate analyses.<h4>Results</h4>In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group.<h4>Conclusions</h4>A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.
format	article
author	Erika J Lampert Kingshuk Roy Choudhury Christopher A Hostage Jeffrey R Petrella P Murali Doraiswamy Alzheimer’s Disease Neuroimaging Initiative
author_facet	Erika J Lampert Kingshuk Roy Choudhury Christopher A Hostage Jeffrey R Petrella P Murali Doraiswamy Alzheimer’s Disease Neuroimaging Initiative
author_sort	Erika J Lampert
title	Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
title_short	Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
title_full	Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
title_fullStr	Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
title_full_unstemmed	Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
title_sort	prevalence of alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f00228b9b6e04b159ff04337c0d55f52
work_keys_str_mv	AT erikajlampert prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives AT kingshukroychoudhury prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives AT christopherahostage prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives AT jeffreyrpetrella prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives AT pmuralidoraiswamy prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives AT alzheimersdiseaseneuroimaginginitiative prevalenceofalzheimerspathologicendophenotypesinasymptomaticandmildlyimpairedfirstdegreerelatives
_version_	1718422947206529024

Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

Ejemplares similares