Alzheimer's disease (AD), one of the most devastating neurodegenerative diseases, approximately affects 150 million individuals worldwide and introduces extensive economic burden to modern society. Alzheimer's disease is an irreversible, progressive brain disorder that is characterized by the degeneration of neurons including the formation of amyloid beta plaques and neurofibrillary or Tau tangles. Patients with Alzheimer's disease will slowly lose memory and thinking skills and eventually, the ability to carry out daily fundamental tasks. Unfortunately, to date, very limited medical options are available for AD patients. In 2023, the FDA approved the first amyloid beta-directed antibody, Leqembi, to reduce the amyloid plaques that form in the brain, a defining pathophysiological feature of the disease. However, this medicine is only effective for patients with mild cognitive impairment or at the mild dementia stage of AD. Besides, it cannot improve the pathogenesis of the disease but only slow down the progression of early Alzheimer’s disease. Therefore, a novel therapeutic target is urgently needed for the treatment of AD, which will improve the daily life quality for millions of patients. Among the extensive studies on AD, accumulating evidence indicates that AD is not only a neurological disease but also a neuroinflammatory disorder that involves the dysfunctions of the innate immune system both in the brain and periphery. In particular, the critical roles of CNS and peripheral innate immune cells (e.g., microglia, astrocytes, monocytes, granulocytes, and dendritic cells et al.), peripheral inflammation (inflammation in the blood, intestinal inflammation et al.), and multiple innate immune receptors (i.e. DAMP sensors/Pattern recognition receptors (PPRs) such as Triggering receptors expressed on myeloid cells (TREMs), Toll-like receptors (TLRs), C-type lectin receptors and the NOD-like receptors) and innate immune modulators and pathways (such as IL 10, the growth factor TGF-β, the complement cascade et al.) were discovered as pathological factors in AD onset and progression. Therefore, targeting the innate immunity might serve as a promising avenue for the treatment of AD.

In this Research Topic, we aim to explore and highlight the potential therapeutic target for AD - the innate immunity including the CNS/periphery innate immune cells, peripheral inflammation, and immune receptors and modulators that lead to dysfunctions in both CNS and periphery. This Research Topic will shed light on the role and mechanisms of the innate immunity in the initiation, progression, and outcome of AD. Additionally, we also focus on novel neuronal or immune biomarkers to assess the severity of AD.

We welcome submissions of reviews, mini reviews, reports, and original research articles of preclinical and clinical research that cover, but are not limited to the following subtopics:

• The role and mechanisms of innate immune cells, receptors, modulators and signaling (in both CNS and periphery) in the initiation and progression of AD
• How do systemic immune responses affect the CNS (neuronal damage/recovery) and periphery (peripheral organ dysfunctions) in AD?
• Mechanisms of peripheral organ dysfunctions that modulate AD through immune functions, especially the intestinal-brain axis
• The identification of biomarkers in neuroimmunity, peripheral immune responses, and nervous system predicting the progression and severity of AD
• Novel discoveries and clinical trials applying immune therapies in AD
• New technologies application to investigate the neuro-immune responses associated with AD (including but not limited to, single-cell/ human nuclei gene expression, CyTOF, Cytec® Aurora, Cellular metabolism assay and Olink proteomic assay et al.)

Are you interested in contributing a manuscript to this Research Topic?

Therapeutic Target for Alzheimer's Disease – Innate Immunity in Both CNS and Periphery