PMID- 36922858
OWN - NLM
STAT- MEDLINE
DCOM- 20230320
LR  - 20230320
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 20
IP  - 1
DP  - 2023 Mar 15
TI  - Decrease in naturally occurring antibodies against epitopes of Alzheimer's 
      disease (AD) risk gene products is associated with cognitive decline in AD.
PG  - 74
LID - 10.1186/s12974-023-02750-9 [doi]
LID - 74
AB  - BACKGROUND: Naturally occurring antibodies (NAbs) are germline-encoded 
      immunoglobulins that can bind to and clear out self-neo-epitopes as well as 
      apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer's 
      disease (AD) is not well-understood. METHODS: Twenty-eight candidate proteins 
      encoded by AD-associated genes were selected for this study based on a number of 
      selection criteria, including preferential expression in the brain and 
      B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their 
      epitopes in age- and gender-matched cognitively normal subjects (CN, n = 56), 
      subjects with mild cognitive impairment (MCI, n = 16) and subjects with AD 
      (n = 56). We aimed to study the levels of their NAbs in plasma and their 
      associations with cognitive decline in individuals with AD. RESULTS: Of the 28 
      antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, 
      NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity 
      (0.370) at 95% specificity among all 28 tests. Further protein-protein 
      interaction networks and functional enrichment analysis suggested that target 
      genes were enriched in AD-related pathological processes classified under 
      "Alzheimer's disease", "neurodegenerative disease" and "amyloidosis". The 
      "Alzheimer's disease" and "neurodegenerative disease" clusters, which converged 
      on the initial "recognition" step of microglial phagocytosis, showed the best 
      diagnostic performance for AD. CONCLUSIONS: This study suggests a decline in the 
      function of the adaptive immune system in AD, and the levels of circulating NAbs 
      are likely to serve as biomarkers for surveilling the progression of AD.
CI  - (c) 2023. The Author(s).
FAU - Gu, Dongmei
AU  - Gu D
AD  - Clinical Research Division, Dementia Care and Research Center, Peking University 
      Institute of Mental Health (Sixth Hospital), Beijing, China.
AD  - Beijing Dementia Key Lab, NHC Key Laboratory of Mental Health, National Clinical 
      Research Center for Mental Disorders (Peking University), Beijing, China.
FAU - Wang, Luchun
AU  - Wang L
AD  - Clinical Research Division, Dementia Care and Research Center, Peking University 
      Institute of Mental Health (Sixth Hospital), Beijing, China.
AD  - Beijing Dementia Key Lab, NHC Key Laboratory of Mental Health, National Clinical 
      Research Center for Mental Disorders (Peking University), Beijing, China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - Department of Neurology, Tianjin Medical University General Hospital, Tianjin, 
      China. nkzhangnan@yeah.net.
FAU - Wang, Huali
AU  - Wang H
AD  - Clinical Research Division, Dementia Care and Research Center, Peking University 
      Institute of Mental Health (Sixth Hospital), Beijing, China. 
      huali_wang@bjmu.edu.cn.
AD  - Beijing Dementia Key Lab, NHC Key Laboratory of Mental Health, National Clinical 
      Research Center for Mental Disorders (Peking University), Beijing, China. 
      huali_wang@bjmu.edu.cn.
FAU - Yu, Xin
AU  - Yu X
AD  - Clinical Research Division, Dementia Care and Research Center, Peking University 
      Institute of Mental Health (Sixth Hospital), Beijing, China.
AD  - Beijing Dementia Key Lab, NHC Key Laboratory of Mental Health, National Clinical 
      Research Center for Mental Disorders (Peking University), Beijing, China.
LA  - eng
GR  - 81870831/National Nature Science Foundation of China/
GR  - 2021ZD0201805/Science and Technology Innovation 2030-Major Project/
GR  - 2017YFC1311100/National Key Research & Development Project, Ministry of Science 
      and Technology/
GR  - 2018YFC1314200/National Key Research & Development Project, Ministry of Science 
      and Technology/
PT  - Journal Article
DEP - 20230315
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Epitopes)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Biomarkers)
RN  - 0 (Antibodies)
SB  - IM
MH  - Humans
MH  - *Alzheimer Disease/pathology
MH  - Epitopes
MH  - *Cognitive Dysfunction/genetics/diagnosis
MH  - Amyloid beta-Peptides
MH  - *Amyloidosis
MH  - Biomarkers
MH  - Antibodies
MH  - Disease Progression
PMC - PMC10018846
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Immunity
OT  - Natural antibodies
OT  - Phagocytosis
OT  - Plasma biomarkers
COIS- All authors declare no competing interests.
EDAT- 2023/03/17 06:00
MHDA- 2023/03/21 06:00
PMCR- 2023/03/15
CRDT- 2023/03/16 01:58
PHST- 2022/12/19 00:00 [received]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/03/16 01:58 [entrez]
PHST- 2023/03/17 06:00 [pubmed]
PHST- 2023/03/21 06:00 [medline]
PHST- 2023/03/15 00:00 [pmc-release]
AID - 10.1186/s12974-023-02750-9 [pii]
AID - 2750 [pii]
AID - 10.1186/s12974-023-02750-9 [doi]
PST - epublish
SO  - J Neuroinflammation. 2023 Mar 15;20(1):74. doi: 10.1186/s12974-023-02750-9.