TY - JOUR
T1 - Adaptive immune changes associate with clinical progression of Alzheimer's disease
AU - van Olst, Lynn
AU - Kamermans, Alwin
AU - Halters, Sem
AU - van der Pol, Susanne M A
AU - Rodriguez, Ernesto
AU - Verberk, Inge M W
AU - Verberk, Sanne G S
AU - Wessels, Danielle W R
AU - Rodriguez-Mogeda, Carla
AU - Verhoeff, Jan
AU - Wouters, Dorine
AU - Van den Bossche, Jan
AU - Garcia-Vallejo, Juan J
AU - Lemstra, Afina W
AU - Witte, Maarten E
AU - van der Flier, Wiesje M
AU - Teunissen, Charlotte E
AU - de Vries, Helga E
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - BACKGROUND: Alzheimer's disease (AD) is the most frequent cause of dementia. Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.METHODS: We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).RESULTS: We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE ε4 allele on peripheral immunity.CONCLUSIONS: Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.
AB - BACKGROUND: Alzheimer's disease (AD) is the most frequent cause of dementia. Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.METHODS: We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).RESULTS: We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE ε4 allele on peripheral immunity.CONCLUSIONS: Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.
KW - APOE
KW - Adaptive immunity
KW - Alzheimer’s disease
KW - Neuroinflammation
KW - T cells
KW - TEMRA cells
UR - http://www.scopus.com/inward/record.url?scp=85191351548&partnerID=8YFLogxK
U2 - 10.1186/s13024-024-00726-8
DO - 10.1186/s13024-024-00726-8
M3 - Article
C2 - 38658964
SN - 1750-1326
VL - 19
SP - 38
JO - Molecular Neurodegeneration
JF - Molecular Neurodegeneration
IS - 1
M1 - 38
ER -