The Micron Stroke Hypothesis of Alzheimer’s Disease and Dementia

Orehek, Allen J.

doi:10.1016/j.mehy.2012.01.020

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…The increased incidence of AD in patients suffering from hypertension and irregular heartbeat, gave rise to the hypothesis of "micron strokes" [45]. Micro-strokes caused by fibrous eythrocyte emboli or micron-sized cholesterol crystals could act as "seeding points" for the growth of amyloid plaques as a healing response.…”

Section: Alzheimer's Disease and Dementiamentioning

confidence: 99%

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Hamblin

2019

Photonics

103

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Next to cancer, Alzheimer’s disease (AD) and dementia is probably the most worrying health problem facing the Western world today. A large number of clinical trials have failed to show any benefit of the tested drugs in stabilizing or reversing the steady decline in cognitive function that is suffered by dementia patients. Although the pathological features of AD consisting of beta-amyloid plaques and tau tangles are well established, considerable debate exists concerning the genetic or lifestyle factors that predispose individuals to developing dementia. Photobiomodulation (PBM) describes the therapeutic use of red or near-infrared light to stimulate healing, relieve pain and inflammation, and prevent tissue from dying. In recent years PBM has been applied for a diverse range of brain disorders, frequently applied in a non-invasive manner by shining light on the head (transcranial PBM). The present review discusses the mechanisms of action of tPBM in the brain, and summarizes studies that have used tPBM to treat animal models of AD. The results of a limited number of clinical trials that have used tPBM to treat patients with AD and dementia are discussed.

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Section: Alzheimer's Disease and Dementiamentioning

confidence: 99%

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Hamblin

2019

Photonics

103

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“…Soluble Aβ itself could trigger neuronal cell cycle reentry [105]. Tissue-injury-inducing insult, such as stroke, and micro-injury-inducing conditions, such as diabetes or hypertension [106][107][108], represent risk factors for AD [8,23]. Injuries can provoke growth signaling that is normally associated with wound healing and inflammation (Figure 3).…”

Section: Late-onset Accumulation Of Amyloid-beta In Sgo1 Brainmentioning

confidence: 99%

Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

et al. 2018

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From early-onset Alzheimer's disease (EOAD) studies, the amyloid-beta hypothesis emerged as the foremost theory of the pathological causes of AD. However, how amyloid-beta accumulation is triggered and progresses toward senile plaques in spontaneous late-onset Alzheimer's disease (LOAD) in humans remains unanswered. Various LOAD facilitators have been proposed, and LOAD is currently considered a complex disease with multiple causes. Mice do not normally develop LOAD. Possibly due to the multiple causes, proposed LOAD facilitators have not been able to replicate spontaneous LOAD in mice, representing a disease modeling issue. Recently, we reported spontaneous late-onset development of amyloid-beta accumulation in brains of Shugoshin 1 (Sgo1) haploinsufficient mice, a cohesinopathy-mediated chromosome instability model. The result for the first time expands disease relevance of mitosis studies to a major disease other than cancers. Reverse-engineering of the model would shed light on the process of late-onset amyloid-beta accumulation in the brain and spontaneous LOAD development, and contribute to development of interventions for LOAD. This review will discuss the Sgo1 model, our current "three-hit hypothesis" regarding LOAD development with an emphasis on critical role of prolonged mitosis in amyloid-beta accumulation, and implications for human LOAD intervention and treatment. Abbreviations: Alzheimer's disease (AD); Late-onset Alzheimer's disease (LOAD); Early-onset Alzheimer's disease (EOAD); Shugoshin-1 (Sgo1); Chromosome Instability (CIN); apolipoprotein (Apoe); Central nervous system (CNS); Amyloid precursor protein (APP); N-methyl-d-aspartate (NMDA); Hazard ratio (HR); Cyclin-dependent kinase (CDK); Chronic Atrial Intestinal Dysrhythmia (CAID); beta-secretase 1 (BACE); phosphor-Histone H3 (p-H3); Research and development (R&D); Non-steroidal anti-inflammatory drugs (NSAIDs); Brain blood barrier (BBB).

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“…Cardiovascular diseases and ischemic stroke share overlapping genetic and metabolic risk factors such as hypertension, dyslipidemia, glucose intolerance or diabetes and adipositas (Arboix, 2015 ). Recently these risk factors were established to also increase the odds of developing AD (Orehek, 2012 ; Wiesmann et al, 2013 ; Traylor et al, 2016 ). Moreover, hypoxic-ischemic conditions of the brain such as in ischemic stroke (Honig et al, 2003 ), heart arrest (de la Torre, 2006 ), and cerebral small vessel disease (Cai et al, 2015 ) directly correlate with AD risk, suggesting that cerebrovascular dysfunction is one possible cause of the neurodegenerative disease (Humpel, 2011 ; Orehek, 2012 ).…”

Section: Brain Ischemia App and Admentioning

confidence: 99%

“…Recently these risk factors were established to also increase the odds of developing AD (Orehek, 2012 ; Wiesmann et al, 2013 ; Traylor et al, 2016 ). Moreover, hypoxic-ischemic conditions of the brain such as in ischemic stroke (Honig et al, 2003 ), heart arrest (de la Torre, 2006 ), and cerebral small vessel disease (Cai et al, 2015 ) directly correlate with AD risk, suggesting that cerebrovascular dysfunction is one possible cause of the neurodegenerative disease (Humpel, 2011 ; Orehek, 2012 ). Data from a large meta-analysis (Zhou et al, 2015 ) and a longitudinal study with over 6500 participants (Tosto et al, 2016 ) show that ischemic stroke increases AD risk by about 1.6 to 2.2-fold, respectively.…”

Section: Brain Ischemia App and Admentioning

confidence: 99%

APP as a Protective Factor in Acute Neuronal Insults

Hefter

Draguhn

2017

Front. Mol. Neurosci.

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Despite its key role in the molecular pathology of Alzheimer’s disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival. Indeed, different animal models of acute hypoxia-ischemia, traumatic brain injury (TBI) and excitotoxicity have revealed protective effects of APP or APPsα. The underlying mechanisms involve APP-mediated regulation of calcium homeostasis via NMDA receptors (NMDAR), voltage-gated calcium channels (VGCC) or internal calcium stores. In addition, APP affects the expression of survival- or apoptosis-related genes as well as neurotrophic factors. In this review, we summarize the current understanding of the neuroprotective role of APP and APPsα and possible implications for future research and new therapeutic strategies.

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The Micron Stroke Hypothesis of Alzheimer’s Disease and Dementia

Cited by 8 publications

References 37 publications

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

APP as a Protective Factor in Acute Neuronal Insults

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