Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

García‐Morales, Victoria; González-Acedo, Anabel; Melguizo‐Rodríguez, Lucia; Pardo-Moreno, Teresa; Costela‐Ruiz, Víctor J.; Montiel-Troya, Maria; Ramos-Rodríguez, Juan José

doi:10.3390/biomedicines9121910

Cited by 47 publications

(58 citation statements)

References 127 publications

(153 reference statements)

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“…Although a small proportion of AD diagnoses are familial, greater than 97% of all diagnoses are late onset, sporadic AD ( Garcia-Morales et al, 2021 ). Recent efforts to define the continuum of AD pathology from asymptomatic preclinical AD to symptomatic, sporadic AD have elucidated characteristic biomarker changes throughout the spectrum of AD progression.…”

Section: Amyloid-β and Alzheimer’s Diseasementioning

confidence: 99%

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease (AD) is a progressive neurodegenerative condition characterized by clinical decline in memory and other cognitive functions. A classic AD neuropathological hallmark includes the accumulation of amyloid-β (Aβ) plaques, which may precede onset of clinical symptoms by over a decade. Efforts to prevent or treat AD frequently emphasize decreasing Aβ through various mechanisms, but such approaches have yet to establish compelling interventions. It is still not understood exactly why Aβ accumulates in AD, but it is hypothesized that Aβ and other downstream pathological events are a result of impaired bioenergetics, which can also manifest prior to cognitive decline. Evidence suggests that individuals with AD and at high risk for AD have functional brain ketone metabolism and ketotherapies (KTs), dietary approaches that produce ketone bodies for energy metabolism, may affect AD pathology by targeting impaired brain bioenergetics. Cognitively normal individuals with elevated brain Aβ, deemed “preclinical AD,” and older adults with peripheral metabolic impairments are ideal candidates to test whether KTs modulate AD biology as they have impaired mitochondrial function, perturbed brain glucose metabolism, and elevated risk for rapid Aβ accumulation and symptomatic AD. Here, we discuss the link between brain bioenergetics and Aβ, as well as the potential for KTs to influence AD risk and progression.

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Section: Amyloid-β and Alzheimer’s Diseasementioning

confidence: 99%

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

et al. 2022

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“…Alzheimer’s disease is the most common cause of cognitive impairment or dementia in individuals older than 65 years and rising global longevity is leading to a worldwide pandemic of mild cognitive impairment (MCI), AD, and AD-related dementia. There is no cure for AD; however non-pharmacological (e.g., exercise) and pharmacological (e.g., acetylcholinesterase inhibitors) interventions can mitigate the symptoms and attenuate the progression of the disease [ 8 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

“…Therefore, AD dementia is a clinical diagnosis since, for example, 20–40% of individuals aged 70 or above do not have cognitive impairment in the presence of biomarkers for AD, or autopsy evidence of AD pathology. Also, AD-associated pathological brain changes often coexist with other pathologies, for example with VAD, LBD or cerebral amyloid angiopathy and these comorbidities, in conjunction with the presence of modifiable risk factors, contribute to the variety of AD clinical signs and symptoms that increase the complexity for development of effective diagnostic tools and treatment interventions [ 8 , 9 , 20 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Physical Exercise, a Potential Non-Pharmacological Intervention for Attenuating Neuroinflammation and Cognitive Decline in Alzheimer’s Disease Patients

Ribarič

2022

IJMS

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This narrative review summarises the evidence for considering physical exercise (PE) as a non-pharmacological intervention for delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Ageing is the most important risk factor for AD. A hallmark of the ageing process is a systemic low-grade chronic inflammation that also contributes to neuroinflammation. Neuroinflammation is associated with AD, Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders. Pharmacological treatment of AD is currently limited to mitigating the symptoms and attenuating progression of the disease. AD animal model studies and human studies on patients with a clinical diagnosis of different stages of AD have concluded that PE attenuates cognitive decline not only by improving cardiovascular fitness but possibly also by attenuating neuroinflammation. Therefore, low-grade chronic inflammation and neuroinflammation should be considered potential modifiable risk factors for AD that can be attenuated by PE. This opens the possibility for personalised attenuation of neuroinflammation that could also have important health benefits for patients with other inflammation associated brain disorders (i.e., Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders). In summary, life-long, regular, structured PE should be considered as a supplemental intervention for attenuating the progression of AD in human. Further studies in human are necessary to develop optimal, personalised protocols, adapted to the progression of AD and the individual’s mental and physical limitations, to take full advantage of the beneficial effects of PE that include improved cardiovascular fitness, attenuated systemic inflammation and neuroinflammation, stimulated brain Aβ peptides brain catabolism and brain clearance.

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“…Amyloid-β Pathology SP are a classic neuropathological feature in AD-affected brains and remain a feasible origin of synaptic and neuronal loss. SP are the result of a progressive accumulation of parenchymal amyloid-β (Aβ) [5]. Aβ is a 39-43 amino acid peptide derived from the progressive processing of Aβ precursor protein (APP) by βand γ-secretase complexes following an amyloidogenic pathway.…”

Section: Introduction 1epidemiology Of Alzheimer's Diseasementioning

confidence: 99%

Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives

Pardo-Moreno¹,

et al. 2022

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Alzheimer’s disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-β, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aβ pathology and tau pathology, and which include γ-secretase inhibitors, β-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aβ clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease. Therefore, the aim of this review was to analyze and describe current treatments and possible future alternatives in the therapeutic approach to AD.

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Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

Cited by 47 publications

References 127 publications

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

Physical Exercise, a Potential Non-Pharmacological Intervention for Attenuating Neuroinflammation and Cognitive Decline in Alzheimer’s Disease Patients

Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives

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