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Inflammatory aspects of Alzheimer’s disease

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Abstract

Alzheimer´s disease (AD) stands out as the most common chronic neurodegenerative disorder. AD is characterized by progressive cognitive decline and memory loss, with neurodegeneration as its primary pathological feature. The role of neuroinflammation in the disease course has become a focus of intense research. While microglia, the brain’s resident macrophages, have been pivotal to study central immune inflammation, recent evidence underscores the contributions of other cellular entities to the neuroinflammatory process. In this article, we review the inflammatory role of microglia and astrocytes, focusing on their interactions with AD’s core pathologies, amyloid beta deposition, and tau tangle formation. Additionally, we also discuss how different modes of regulated cell death in AD may impact the chronic neuroinflammatory environment. This review aims to highlight the evolving landscape of neuroinflammatory research in AD and underscores the importance of considering multiple cellular contributors when developing new therapeutic strategies.

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Abbreviations

ACT:

Antichymotrypsin

AD:

Alzheimer disease

Aβ:

Amyloid-β

APOE:

Apolipoprotein E

ApoJ/Clusterin:

Apolipoprotein J

ALS:

Amyotrophic lateral sclerosis

ASC:

Apoptosis-associated Speck-like protein containing a CARD

APP:

Amyloid precursor protein

BAMs:

Border-associated macrophages

BBB:

Blood–brain barrier

Bcl:

B-cell lymphoma

BECs:

Brain endothelial cells

C:

Complement component

C1q:

Subcomponent q

CCL:

C–C motif chemokine ligand

CD40L:

CD40 ligand

CDK:

Cyclin-dependent kinase

CNS:

Central nervous system

CN:

Calcineurin

COX:

Cyclooxygenase

DAMPs:

Damage-associated molecular patterns

EOAD:

Early onset familial alzheimer disease

FERMT:

Fermitin family homolog

GFAP:

Glial fibrillary acidic protein

GMF:

Glia maturation factor

GBP:

Guanylate binding protein

GSK:

Glycogen synthase kinase

GWAS:

Genome-wide association studies

HSPs:

Heat shock proteins

HSPGs:

Heparan sulfate proteoglycans

HMGB:

High mobility group box

ICAM-1:

Intercellular adhesion molecule 1

IDE:

Insulin-degrading enzyme

IFN:

Interferon

IL:

Interleukin

iPS:

Induced pluripotent stem

JAK:

Janus kinase

MAPK:

Mitogen-activated protein kinase

MMP9:

Matrix metalloprotease 9

MLKL:

Mixed lineage kinase domain-like

MMP:

Matrix metalloproteinase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NDDs:

Neurodegenerative diseases

NEP:

Neprylisin

NFAT:

Nuclear factor of activated T cells

NFκB:

Nuclear factor-κB

NLRs:

Nucleotide-binding oligomerization domain-like receptors

NFTs:

Neurofibrillary tangles

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOD:

Nucleotide-binding oligomerization domain

PAR:

Protease-activated receptors

PAMPs:

Pathogen-associated molecular patterns

PD:

Parkinson’s disease

PDGFRβ:

Platelet-derived growth factor receptor β

PG:

Prostaglandin

PKs:

Protein kinases

PFFs:

Preformed fibrils

PRRs:

Pattern recognition receptors

PSEN:

Presenilin

PVMs:

Perivascular macrophages

RIPK:

Receptor-interactive protein kinases

RAGE:

Receptor for advanced glycation end products

RB:

Retinoblastoma

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

RCD:

Regulated cell death

SAM:

Senescent-associated microglia

SASP:

Senescence-associated secretory phenotype

SAHF:

Senescence-associated heterochromatin foci

SORL:

Sortilin-related receptor

SP:

Substance P

STAT:

Signal transducer and activator of transcription

SRs:

Scavenger receptors

TNTs:

Tunnelling nanotubes

TNF:

Tumor necrosis factor

TRAIL:

TNF-related apoptosis-inducing ligand

TREM:

Triggering receptor expressed on myeloid cells

TGF:

Transforming growth factor

TLRs:

Toll-like receptors

VEGF:

Vascular endothelial growth factor

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  1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing, Belvaux, L-4367, Esch-Belval, Luxembourg

    Pablo Botella Lucena & Michael T. Heneka

  2. Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA

    Michael T. Heneka

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Botella Lucena, P., Heneka, M.T. Inflammatory aspects of Alzheimer’s disease. Acta Neuropathol 148, 31 (2024). https://doi.org/10.1007/s00401-024-02790-2

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