TY - JOUR
T1 - Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer's Disease in Non-Demented Elderly
AU - Slot, Rosalinde E R
AU - Van Harten, Argonde C.
AU - Kester, Maartje I.
AU - Jongbloed, Wesley
AU - Bouwman, Femke H.
AU - Teunissen, Charlotte E.
AU - Scheltens, Philip
AU - Veerhuis, Robert
AU - Van Der Flier, Wiesje M.
PY - 2017
Y1 - 2017
N2 - Background: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer's disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. Objective: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. Methods: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n=206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n=223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOE ϵ4 carriership. Results: 117 patients (27) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30 increased risk of clinical progression (hazard ratio (HR) (95 CI) =1.3(1.0-1.6)). The effect appeared to be attributable to the APOE ϵ4 carriers with SCD (HR 3.3(1.0-10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ϵ4 carriers with SCD (HR 5.0(1.3-18.9)). Conclusion: Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ϵ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.
AB - Background: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer's disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. Objective: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. Methods: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n=206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n=223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOE ϵ4 carriership. Results: 117 patients (27) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30 increased risk of clinical progression (hazard ratio (HR) (95 CI) =1.3(1.0-1.6)). The effect appeared to be attributable to the APOE ϵ4 carriers with SCD (HR 3.3(1.0-10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ϵ4 carriers with SCD (HR 5.0(1.3-18.9)). Conclusion: Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ϵ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - Apolipoprotein-A1
KW - mild cognitive impairment
KW - subjective cognitive decline
UR - http://www.scopus.com/inward/record.url?scp=85011423465&partnerID=8YFLogxK
U2 - https://doi.org/10.3233/JAD-151068
DO - https://doi.org/10.3233/JAD-151068
M3 - Article
C2 - 28035918
SN - 1387-2877
VL - 56
SP - 687
EP - 697
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -