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

Giannisis, Andreas ; Al-Grety, Asma ; Carlsson, Henrik ; Patra, Kalicharan ; Twohig, Daniel LU orcid ; Sando, Sigrid Botne ; Lauridsen, Camilla ; Berge, Guro ; Grøntvedt, Gøril Rolfseng and Bråthen, Geir , et al. (2022) In Alzheimer's Research & Therapy 14(1).
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.

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 =... (More)

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.

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.

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 (Aβ42) 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 Aβ42, 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.

CONCLUSIONS: Our results demonstrate important associations between low plasma apoE levels, Aβ pathology, and progression from aMCI to a clinical ADD diagnosis.

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Contribution to journal
publication status
published
keywords
Alzheimer Disease/cerebrospinal fluid, Amyloid beta-Peptides/cerebrospinal fluid, Apolipoprotein E3/cerebrospinal fluid, Apolipoprotein E4/cerebrospinal fluid, Apolipoproteins E/cerebrospinal fluid, Biomarkers/cerebrospinal fluid, Cognitive Dysfunction/cerebrospinal fluid, Female, Humans, Kallikreins, Peptide Fragments/cerebrospinal fluid, alpha-Synuclein, tau Proteins/cerebrospinal fluid
in
Alzheimer's Research & Therapy
volume
14
issue
1
article number
115
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85136522928
  • pmid:36002891
ISSN
1758-9193
DOI
10.1186/s13195-022-01058-9
language
English
LU publication?
no
additional info
© 2022. The Author(s).
id
1c776faa-86cd-4f80-b8bd-c3c7fe1473ef
date added to LUP
2024-05-08 13:56:54
date last changed
2024-11-07 23:50:57
@article{1c776faa-86cd-4f80-b8bd-c3c7fe1473ef,
  abstract     = {{<p>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.</p><p>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.</p><p>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 (Aβ42) 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 Aβ42, 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.</p><p>CONCLUSIONS: Our results demonstrate important associations between low plasma apoE levels, Aβ pathology, and progression from aMCI to a clinical ADD diagnosis.</p>}},
  author       = {{Giannisis, Andreas and Al-Grety, Asma and Carlsson, Henrik and Patra, Kalicharan and Twohig, Daniel and Sando, Sigrid Botne and Lauridsen, Camilla and Berge, Guro and Grøntvedt, Gøril Rolfseng and Bråthen, Geir and White, Linda R and Kultima, Kim and Nielsen, Henrietta M}},
  issn         = {{1758-9193}},
  keywords     = {{Alzheimer Disease/cerebrospinal fluid; Amyloid beta-Peptides/cerebrospinal fluid; Apolipoprotein E3/cerebrospinal fluid; Apolipoprotein E4/cerebrospinal fluid; Apolipoproteins E/cerebrospinal fluid; Biomarkers/cerebrospinal fluid; Cognitive Dysfunction/cerebrospinal fluid; Female; Humans; Kallikreins; Peptide Fragments/cerebrospinal fluid; alpha-Synuclein; tau Proteins/cerebrospinal fluid}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research & Therapy}},
  title        = {{Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1186/s13195-022-01058-9}},
  doi          = {{10.1186/s13195-022-01058-9}},
  volume       = {{14}},
  year         = {{2022}},
}