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Perspectives on the Tertiary Prevention Strategy for Alzheimer ’ s Disease

View Article: PubMed Central - PubMed

ABSTRACT

Amyloid-beta (Aβ) plays a pivotal role in Alzheimer’s disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Aβ-targeting clinical trials, however, has prompted questions on whether Aβ is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Aβ alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Aβ and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD.

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Pathophysiological abnormalities and management of stroke and AD. The development of AD is similar to that of stroke. Both diseases start at mid-life and affect the elderly and can be divided into presymptomatic, TIA/MCI and stroke/AD dementia stages. Aβ and various risk factors for AD are analogous to the vascular risk factors for stroke; they, like vascular risk factors, represent the etiology of the disease. Both diseases have different pathophysiological abnormalities and, correspondingly, different therapeutic targets at different stages of the diseases. Abbreviations: Aβ, amyloid-β; TIA, transient ischemic attack; MCI, mild cognitive impairment; phos-Tau, phosphorylated Tau
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Figure 1: Pathophysiological abnormalities and management of stroke and AD. The development of AD is similar to that of stroke. Both diseases start at mid-life and affect the elderly and can be divided into presymptomatic, TIA/MCI and stroke/AD dementia stages. Aβ and various risk factors for AD are analogous to the vascular risk factors for stroke; they, like vascular risk factors, represent the etiology of the disease. Both diseases have different pathophysiological abnormalities and, correspondingly, different therapeutic targets at different stages of the diseases. Abbreviations: Aβ, amyloid-β; TIA, transient ischemic attack; MCI, mild cognitive impairment; phos-Tau, phosphorylated Tau

Mentions: At present, most multi-factorial and complex diseases are managed by tertiary prevention strategy, which includes the primary, secondary and tertiary prevention. Primary disease prevention aims to prevent disease or injury of before it occurs either through eliminating disease-modifiable risk factors or increasing resistance to disease, including immunization against diseases, and maintaining a healthy diet and lifestyle. Secondary disease prevention aims to detect and address an existing disease or injury prior to the appearance of symptoms, including screening tests to detect disease in its earliest stages and treating the disease or injury to prevent further progression. Tertiary disease prevention aims to improve the patient’s quality of life by softening the negative impacts of an ongoing symptomatic disease. This approach includes rehabilitation and treatment methods that halt disease progression. In line with this, we proposed the tertiary prevention strategy for AD (Fig. 1). Avoiding systemic diseases, sleep disorders and environmental risk factors, maintaining healthy diet and exercise, and preventing the production of Aβ at the preclinical stage should represent the primary methods for AD prevention. Current therapeutics focuses on the removal of Aβ plaques, the protection of synaptic function and neurons, and the attenuation of tau hyperphosphorylation at the MCI stage, called secondary prevention. For symptomatic AD patients, not only Aβ but also other pathological pathways, such as tau hyperphosphorylation, neuroinflammation, oxidative stress and synaptic injury, should be targeted (tertiary prevention or treatment).


Perspectives on the Tertiary Prevention Strategy for Alzheimer ’ s Disease
Pathophysiological abnormalities and management of stroke and AD. The development of AD is similar to that of stroke. Both diseases start at mid-life and affect the elderly and can be divided into presymptomatic, TIA/MCI and stroke/AD dementia stages. Aβ and various risk factors for AD are analogous to the vascular risk factors for stroke; they, like vascular risk factors, represent the etiology of the disease. Both diseases have different pathophysiological abnormalities and, correspondingly, different therapeutic targets at different stages of the diseases. Abbreviations: Aβ, amyloid-β; TIA, transient ischemic attack; MCI, mild cognitive impairment; phos-Tau, phosphorylated Tau
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997925&req=5

Figure 1: Pathophysiological abnormalities and management of stroke and AD. The development of AD is similar to that of stroke. Both diseases start at mid-life and affect the elderly and can be divided into presymptomatic, TIA/MCI and stroke/AD dementia stages. Aβ and various risk factors for AD are analogous to the vascular risk factors for stroke; they, like vascular risk factors, represent the etiology of the disease. Both diseases have different pathophysiological abnormalities and, correspondingly, different therapeutic targets at different stages of the diseases. Abbreviations: Aβ, amyloid-β; TIA, transient ischemic attack; MCI, mild cognitive impairment; phos-Tau, phosphorylated Tau
Mentions: At present, most multi-factorial and complex diseases are managed by tertiary prevention strategy, which includes the primary, secondary and tertiary prevention. Primary disease prevention aims to prevent disease or injury of before it occurs either through eliminating disease-modifiable risk factors or increasing resistance to disease, including immunization against diseases, and maintaining a healthy diet and lifestyle. Secondary disease prevention aims to detect and address an existing disease or injury prior to the appearance of symptoms, including screening tests to detect disease in its earliest stages and treating the disease or injury to prevent further progression. Tertiary disease prevention aims to improve the patient’s quality of life by softening the negative impacts of an ongoing symptomatic disease. This approach includes rehabilitation and treatment methods that halt disease progression. In line with this, we proposed the tertiary prevention strategy for AD (Fig. 1). Avoiding systemic diseases, sleep disorders and environmental risk factors, maintaining healthy diet and exercise, and preventing the production of Aβ at the preclinical stage should represent the primary methods for AD prevention. Current therapeutics focuses on the removal of Aβ plaques, the protection of synaptic function and neurons, and the attenuation of tau hyperphosphorylation at the MCI stage, called secondary prevention. For symptomatic AD patients, not only Aβ but also other pathological pathways, such as tau hyperphosphorylation, neuroinflammation, oxidative stress and synaptic injury, should be targeted (tertiary prevention or treatment).

View Article: PubMed Central - PubMed

ABSTRACT

Amyloid-beta (Aβ) plays a pivotal role in Alzheimer’s disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Aβ-targeting clinical trials, however, has prompted questions on whether Aβ is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Aβ alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Aβ and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD.

No MeSH data available.


Related in: MedlinePlus