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Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer's disease.

Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer's disease.

Authors :
Giannisis A
Al-Grety A
Carlsson H
Patra K
Twohig D
Sando SB
Lauridsen C
Berge G
Grøntvedt GR
Bråthen G
White LR
Kultima K
Nielsen HM
Source :
Alzheimer's research & therapy [Alzheimers Res Ther] 2022 Aug 24; Vol. 14 (1), pp. 115. Date of Electronic Publication: 2022 Aug 24.
Publication Year :
2022

Abstract

Background: Low levels of plasma apolipoprotein E (apoE) and presence of the APOE ε4 allele are associated with an increased risk of Alzheimer's disease (AD). Although the increased risk of AD in APOE ε4-carriers is well-established, the protein levels have received limited attention.<br />Methods: We here report the total plasma apoE and apoE isoform levels at baseline from a longitudinally (24 months) followed cohort including controls (n = 39), patients with stable amnestic mild cognitive impairment during 24 months follow up (MCI-MCI, n = 30), patients with amnestic MCI (aMCI) that during follow-up were clinically diagnosed with AD with dementia (ADD) (MCI-ADD, n = 28), and patients with AD with dementia (ADD) at baseline (ADD, n = 28). We furthermore assessed associations between plasma apoE levels with cerebrospinal fluid (CSF) AD biomarkers and α-synuclein, as well as both CSF and plasma neurofilament light chain (NfL), YKL-40 and kallikrein 6.<br />Results: Irrespective of clinical diagnosis, the highest versus the lowest apoE levels were found in APOE ε2/ε3 versus APOE ε4/ε4 subjects, with the most prominent differences exhibited in females. Total plasma apoE levels were 32% and 21% higher in the controls versus MCI-ADD and ADD patients, respectively. Interestingly, MCI-ADD patients exhibited a 30% reduction in plasma apoE compared to MCI-MCI patients. This decrease appeared to be associated with brain amyloid-β (Aβ <subscript>42</subscript> ) pathology regardless of disease status as assessed using the Amyloid, Tau, and Neurodegeneration (A/T/N) classification. In addition to the association between low plasma apoE and low levels of CSF Aβ <subscript>42</subscript> , lower apoE levels were also related to higher levels of CSF total tau (t-tau) and tau phosphorylated at Threonine 181 residue (p-tau) and NfL as well as a worse performance on the mini-mental-state-examination. In MCI-ADD patients, low levels of plasma apoE were associated with higher levels of CSF α-synuclein and kallikrein 6. No significant correlations between plasma apoE and the astrocytic inflammatory marker YKL40 were observed.<br />Conclusions: Our results demonstrate important associations between low plasma apoE levels, Aβ pathology, and progression from aMCI to a clinical ADD diagnosis.<br /> (© 2022. The Author(s).)

Details

Language :
English
ISSN :
1758-9193
Volume :
14
Issue :
1
Database :
MEDLINE
Journal :
Alzheimer's research & therapy
Publication Type :
Academic Journal
Accession number :
36002891
Full Text :
https://doi.org/10.1186/s13195-022-01058-9