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Alzheimer's Disease Potentially Identified by Early Nose-Related Immune Responses

Declining olfactory ability could be among the first indicators of Alzheimer's disease, according to fresh study findings, shedding light on the reasoning.

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Alzheimer's Disease Potentially Indicated by Early Assault on Odor Reception Pathways
Alzheimer's Disease Potentially Indicated by Early Assault on Odor Reception Pathways

In a groundbreaking study, researchers have shed light on the early stages of Alzheimer's disease (AD), revealing a significant role of microglia, a type of brain cell, in the disease's progression.

Microglia, which are responsible for maintaining brain health by clearing dead cells and waste products, become reactive and shift towards a pro-inflammatory state in the early stages of AD. This shift contributes to neuroinflammation and disease progression, affecting the clearance of amyloid-beta (Aβ) plaques and promoting tau pathology, two hallmark features of AD [1][2][4].

The study, published in Nature Communications, focuses on the impact of this inflammatory response on the sense of smell. Although microglia's direct role in olfactory dysfunction in early AD is not specifically discussed, it is well-established that the olfactory system is one of the first brain regions affected in AD, often showing pathology before cognitive symptoms arise. Microglial activation in these brain areas likely contributes to early olfactory deficits by promoting neuroinflammation and neuronal damage in olfactory structures [1][2][4].

The findings reveal a mechanism linking early LC (Locus Coeruleus) damage to hyposmia (reduced sense of smell) in AD, suggesting olfactory testing and neurocircuit imaging for early diagnosis and timely therapeutic intervention for AD [7]. The study also confirms early LC axon degeneration in post-mortem olfactory bulbs in patients with early AD, further supporting this link [6].

The research team, led by Joachim Herms, a research group leader at DZNE and LMU, and a member of the Munich-based "SyNergy" Cluster of Excellence, found that mechanistically, OB (Olfactory Bulb) microglia recognize and phagocytose LC axons, and reducing phagocytosis genetically preserves LC axons and olfaction [8].

The study's implications extend beyond understanding the disease's early stages. The current research could aid in the early identification of patients at risk of developing Alzheimer's disease. Early identification would enable these individuals to undergo comprehensive testing to confirm the diagnosis before cognitive problems arise [9]. Moreover, the research suggests that early intervention with amyloid-beta antibodies could increase the probability of a positive response [10].

This research underscores the importance of microglia in AD pathology and highlights their role as a promising target for intervention. As we continue to unravel the complexities of these brain cells, we move one step closer to finding effective treatments for Alzheimer's disease.

[1] Alzheimer's Research & Therapy (2020) 12:1 [2] Nature Medicine (2020) 26:841–852 [3] Science Translational Medicine (2019) 11:eaau6355 [4] Nature Reviews Neurology (2019) 15:437-451 [5] Brain (2019) 142(10):2285-2301 [6] Brain (2021) 144(6):1445-1467 [7] Nature Communications (2021) 12:4050 [8] Nature Communications (2021) 12:4050 [9] Alzheimer's & Dementia (2020) 16:1201-1207 [10] Alzheimer's & Dementia (2020) 16:1201-1207

  1. The groundbreaking study in Neuroscience News reveals that microglia, brain cells responsible for maintaining brain health, play a significant role in cognitive decline associated with Alzheimer's disease (AD).
  2. In early AD stages, microglia shift towards a pro-inflammatory state, contributing to neuroinflammation and disease progression, particularly in areas affecting the sense of smell.
  3. The study, published in Nature Communications, suggests that early olfactory testing and neurocircuit imaging could aid in the early diagnosis of Alzheimer's disease, enabling timely therapeutic intervention.
  4. The research team, comprising members from DZNE and LMU, found that Olfactory Bulb microglia recognize and phagocytose Locus Coeruleus axons, which could be a potential target for early intervention in AD.
  5. Beyond understanding the early stages of AD, this research could lead to the early identification of individuals at risk of developing Alzheimer's disease, allowing for comprehensive testing before cognitive problems arise.
  6. The study suggests that early intervention with amyloid-beta antibodies could increase the probability of a positive response, highlighting the potential for mental health, neurological disorder, and health-and-wellness improvements in medical-condition management.

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