Inflammation in Alzheimer’s disease: insights from immunotherapy

Synopsis Clinicians can diagnose the syndromes of dementia (major neurocognitive disorder) and mild cognitive impairment (mild neurocognitive disorder) based on history, examination, and appropriate objective assessments, using standard criteria such as DSM-5. They can then diagnose the etiological subtypes of these syndromes using standard criteria for each of them. Brain imaging and biomarkers are gaining ground for the differential diagnoses among the different disorders. Treatments for the most part are still symptomatic.

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“…3233 Multiple mechanisms have been proposed for the role played by inflammation in the neuropathology of AD. 343536 …”

Section: Introductionmentioning

confidence: 99%

Dementia and Cognitive Impairment

Hugo

Ganguli

2014

Clinics in Geriatric Medicine

644

254

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“…Microgliosis, astrogliosis, and peripheral immune infiltration contribute to the cognitive and motor deficits, and lead to a toxic increase in the levels of reactive oxygen species [68], and to secondary neurodegeneration, characteristic of late disease stages [69]. Immunotherapy has been shown to induce a physiological microglial response (M2 type) and reduce the production of proinflammatory cytokines [65,66], thus exerting an anti-inflammatory effect in neurodegenerative disorders [70,71]. However, among the disadvantages of immunotherapy are the potential for autoimmune responses, nonspecific inflammatory reactions such as perivascular edema, need for repetitive administration, lack of response due to senescence of the innate immune system, and limited penetration of antibodies into the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders

2016

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Disease-modifying alternatives are sorely needed for the treatment of neurodegenerative disorders, a group of diseases that afflict approximately 50 million Americans annually. Immunotherapy is one of the most developed approaches in this direction. Vaccination against amyloid-β, α-synuclein, or tau has been extensively explored, specially as the discovery that these proteins may propagate cell-to-cell and be accessible to antibodies when embedded into the plasma membrane or in the extracellular space. Likewise, the use of passive immunization approaches with specific antibodies against abnormal conformations of these proteins has also yielded promising results. The clinical development of immunotherapies for Alzheimer's disease, Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, and other neurodegenerative disorders is a field in constant evolution. Results to date suggest that immunotherapy is a promising therapeutic approach for neurodegenerative diseases that progress with the accumulation and prion-like propagation of toxic protein aggregates. Here we provide an overview of the most novel and relevant immunotherapeutic advances targeting amyloid-β in Alzheimer's disease, α-synuclein in Alzheimer's disease and Parkinson's disease, and tau in Alzheimer's disease and frontotemporal dementia.

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“…Despite the significant progress that has been made in identifying inflammation as a core feature of AD, many fundamental questions remain. For instance, it is as yet unclear what aspects of the inflammatory response contribute to the pathological process in AD (Schott and Revesz, 2013).…”

Section: Introductionmentioning

confidence: 99%