Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease

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T1 - Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease

AU - Mattsson, Niklas

AU - Eriksson, Oscar

AU - Lindberg, Olof

AU - Schöll, Michael

AU - Lampinen, Björn

AU - Nilsson, Markus

AU - Insel, Philip S.

AU - Lautner, Ronald

AU - Strandberg, Olof

AU - van Westen, Danielle

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Palmqvist, Sebastian

AU - Stomrud, Erik

AU - Hansson, Oskar

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.

AB - Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.

KW - Alzheimer's disease

KW - APOE

KW - Biomarkers

KW - Cognition

KW - Imaging

KW - Prodromal

U2 - 10.1016/j.neurobiolaging.2018.07.003

DO - 10.1016/j.neurobiolaging.2018.07.003

M3 - Article

VL - 71

SP - 81

EP - 90

JO - Neurobiology of Aging

T2 - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 1558-1497

ER -