To investigate the immunophenotype and function of CD4+ and CD8+ T cells in early stages of Alzheimer's Disease (AD), specifically preclinical AD and mild cognitive impairment (MCI), to better understand their roles in disease progression.
Key Findings:
Preclinical AD subjects can mount a CD4+ T helper cell response towards amyloid-β peptide, suggesting a potential protective mechanism.
Increased CD8+ T effector memory cells re-expressing CD45RA (TEMRA cells) are found in CSF of preclinical AD subjects, indicating altered immune responses.
MCI subjects show increased frequencies of CD8+ TEMRA/effector cells with a pro-inflammatory gene expression profile and decreased antigen responsiveness, which may contribute to disease progression.
Interpretation:
The adaptive immune response in early AD is complex, with potentially beneficial CD4+ T-cell responses in preclinical AD and harmful CD8+ T-cell responses in MCI, highlighting the need for targeted therapeutic strategies.
Limitations:
Cross-sectional design limits causal inferences, making it difficult to establish direct relationships between T-cell responses and disease progression.
Study populations may not fully represent the broader AD population, which could affect the generalizability of the findings.
Conclusion:
Promoting specific CD4+ T-cell responses in preclinical AD may be beneficial, while targeting CD8+ T-cell responses in MCI could be necessary if they are found to be harmful, underscoring the importance of further research in this area.
by Chiara Rickenbach, Anna Mallone, Lars Häusle, Larissa Frei, Sarina Seiter, Colin Sparano, Tunahan Kirabali, Kaj Blennow, Henrik Zetterberg, Maria Teresa Ferretti, Luka Kulic, Christoph Hock, Roger M Nitsch, Valerie Treyer, Anton Gietl, Christoph Gericke
