Peripheral blood amyloid-β involved in the pathogenesis of Alzheimer’s disease via impacting on peripheral innate immune cells

Abstract

A key pathological factor of Alzheimer’s disease (AD), the most prevalent form of age-related dementia in the world, is excessive β-amyloid protein (Aβ) in extracellular aggregation in the brain. And in the peripheral blood, a large amount of Aβ is derived from platelets. So far, the causality between the levels of peripheral blood Aβ and its aggregation in the brain, particularly the role of the peripheral blood Aβ in the pathology of AD, is still unclear. And the relation between the peripheral blood Aβ and tau tangles of brain, another crucial pathologic factor contributing to the pathogenesis of AD, is also ambiguous. More recently, the anti-Aβ monoclonal antibodies are approved for treatment of AD patients through declining the peripheral blood Aβ mechanism of action to enhance plasma and central nervous system (CNS) Aβ clearance, leading to a decrease Aβ burden in brain and improving cognitive function, which clearly indicates that the levels of the peripheral blood Aβ impacted on the Aβ burden in brain and involved in the pathogenesis of AD. In addition, the role of peripheral innate immune cells in AD remains mostly unknown and the results obtained were controversial. In the present review, we summarize recent studies on the roles of peripheral blood Aβ and the peripheral innate immune cells in the pathogenesis of AD. Finally, based on the published data and our own work, we believe that peripheral blood Aβ plays an important role in the development and progression of AD by impacting on the peripheral innate immune cells.

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

“…AD is acknowledged as the most common type of NDS, affecting more than 50 million people worldwide, and is characterized by the brain accumulation of extracellular Aβ aggregates (plaques) and intraneuronal Tau deposits (neurofibrillary tangles) . As an incurable and advancing condition, AD is distinguished by two principal molecular processes: the cholinergic hypothesis, which is associated with the degeneration of cholinergic neurons in the frontal region of the brain, and the amyloid β protein hypothesis, which is linked to the deposition of this protein and the resultant oxidative stress. , AD is also strongly associated with dementia and is caused by various mechanisms, including mitochondrial dysfunction, apoptosis, endoplasmic reticulum stress, genetic factors, oxidative stress, neuroinflammation, microRNA signaling dysregulation, and cholinergic dysfunction, which collectively contribute to the progression of the disease, leading to NDs and cell death as they mutually influence one another. ,− Current treatments, including medications such as tacrine, rivastigmine, galantamine, donepezil, and memantine, aim to alleviate symptoms but do not effectively delay the progression of the disease. − Given the substantial social and economic impact of this disease, it is imperative to redirect treatment efforts toward addressing the diverse mechanisms of neuronal degeneration implicated in its development.…”

“…67 As an incurable and advancing condition, AD is distinguished by two principal molecular processes: the cholinergic hypothesis, which is associated with the degeneration of cholinergic neurons in the frontal region of the brain, and the amyloid β protein hypothesis, which is linked to the deposition of this protein and the resultant oxidative stress. 68,69 AD is also strongly associated with dementia and is caused by various mechanisms, including mitochondrial dysfunction, apoptosis, endoplasmic reticulum stress, genetic factors, oxidative stress, neuroinflammation, microRNA signaling dysregulation, and cholinergic dysfunction, which collectively contribute to the progression of the disease, leading to NDs and cell death as they mutually influence one another. 60,70−73 Current treatments, including medications such as tacrine, rivastigmine, galantamine, donepezil, and memantine, aim to alleviate symptoms but do not effectively delay the progression of the disease.…”