Myeloid cells in vascular dementia and Alzheimer’s disease: Possible therapeutic targets?

García-Culebras A, Cuartero MI, Peña-Martínez C et al. Br J Pharmacol. 2024 Mar;181(6):777-798. doi: 10.1111/bph.16159. Epub 2023 Jul 7. PMID: 37282844

Abstract: Growing evidence supports the suggestion that the peripheral immune system playsa role in different pathologies associated with cognitive impairment, such as vasculardementia (VD) or Alzheimer’s disease (AD). The aim of this review is to summarize,within the peripheral immune system, the implications of different types of myeloidcells in AD and VD, with a special focus on post-stroke cognitive impairment anddementia (PSCID). We will review the contributions of the myeloid lineage, fromperipheral cells (neutrophils, platelets, monocytes and monocyte-derived macro-phages) to central nervous system (CNS)-associated cells (perivascular macrophagesand microglia). Finally, we will evaluate different potential strategies for pharmacolog-ical modulation of pathological processes mediated by myeloid cell subsets, with anemphasis on neutrophils, their interaction with platelets and the process of immuno-thrombosis that triggers neutrophil-dependent capillary stall and hypoperfusion, as possible effector mechanisms that may pave the way to novel therapeutic avenues tostop dementia, the epidemic of our time.

Funding: This work was supported by grants from Spanish Ministry of Scienceand Innovation (MCIN) PID2019-106581RB-I00 (MAM), from LeducqFoundation for Cardiovascular Research TNE19CVD01 (MAM, AGCand MIC) and TNE-21CVD04 (IL and MAM), from Instituto de SaludCarlos III (ISCIII) and co-financed by the European Development Regional Fund “A Way to Achieve Europe”PI20/00535 and RICORS-ICTUSRD21/0006/0001 (IL). CNIC is supported by ISCIII. The CNIC isa Severo Ochoa Center of Excellence (CEX2020-001041-S

The role of gut microbiota in cerebrovascular disease and related dementia

Cuartero MI, García-Culebras A, Nieto-Vaquero C et al.  Br J Pharmacol. 2024 Mar;181(6):816-839. doi: 10.1111/bph.16167. Epub 2023 Jul 12.. PMID: 37328270

Abstract: In recent years, increasing evidence suggests that commensal microbiota may play animportant role not only in health but also in disease including cerebrovascular dis-ease. Gut microbes impact physiology, at least in part, by metabolizing dietary factorsand host-derived substrates and then generating active compounds including toxins.The purpose of this current review is to highlight the complex interplay betweenmicrobiota, their metabolites. and essential functions for human health, ranging fromregulation of the metabolism and the immune system to modulation of brain devel-opment and function. We discuss the role of gut dysbiosis in cerebrovascular disease,specifically in acute and chronic stroke phases, and the possible implication of intesti-nal microbiota in post-stroke cognitive impairment and dementia, and we identifypotential therapeutic opportunities of targeting microbiota in this context.

Funding: This work was supported by grants from the Spanish Ministry ofScience and Innovation (Ministerio de Ciencia e Innovacion [MCIN])(PID2019-106581RB-I00 [MAM] and PID2020-117765RB-I00 [JP]),from Leducq Foundation for Cardiovascular Research (TNE19CVD01[MAM and MIC] and TNE-21CVD04 [MAM and IL]) and from Insti-tuto de Salud Carlos III (ISCIII) and co-financed by the EuropeanDevelopment Regional Fund‘A Way to Achieve Europe’(PI20/00535) and RICORS-ICTUS (RD21/0006/0001 [IL]). CNIC issupported by ISCIII, MCIN and ProCNIC Foundation and is a SeveroOchoa Center of Excellence (CEX2020-001041-S)