Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse

Frère, Samuel; Slutsky, Inna

doi:10.1016/j.neuron.2017.11.028

Cited by 198 publications

(182 citation statements)

References 398 publications

(473 reference statements)

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“…Another incompletely explored aspect is the fact that homeostatic mechanisms seem to fail in AD. Irrespective of the kind of perturbation, neurons and neural circuits are typically bound to maintain a given average firing rate through processes collectively termed integrated homeostatic network 43 . Possible reasons underlying an ineffective homeostatic response could involve a failure of the sensing or effecting machinery.…”

Section: Impact Of Amyloid Plaque Proximitymentioning

confidence: 99%

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

Korzhova

Marinković

Goltstein

et al. 2019

Preprint

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Alzheimer's disease (AD) is associated with aberrant neuronal activity levels. How those activity alterations emerge and how stable they are over time in vivo, however, remains elusive to date. To address these questions we chronically recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice and their non-transgenic littermates over the course of 4 weeks by means of calcium imaging. Surprisingly, aberrant neuronal activity was very stable over time. Moreover, we identified a slow progressive gain of activity of former intermediately active neurons as the main source of new highly active neurons. Interestingly, fluctuations in neuronal activity were independent from amyloid plaque proximity, but aberrant activity levels were more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in AD patients is the consequence of stable single cell aberrant neuronal activity, a finding of potential therapeutic relevance.

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Section: Impact Of Amyloid Plaque Proximitymentioning

confidence: 99%

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

Korzhova

Marinković

Goltstein

et al. 2019

Preprint

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“…Just over 70% of patients with cognitive disease in this study received a diagnosis of AD, the most common cognitive disease in Japan . Neurodegenerative diseases like AD are progressive in nature and have no known essential cure . This lack makes early detection and diagnosis all the more important .…”

Section: Discussionmentioning

confidence: 98%

“…4,5 Neurodegenerative diseases like AD are progressive in nature and have no known essential cure. 6,17 This lack makes early detection and diagnosis all the more important. 5,6 However, multiple barriers stand in the way of timely visits to memory clinics in Japan.…”

Section: Discussionmentioning

confidence: 99%

Japanese Old Stories Cognitive Scale: a screening test to detect cognitive disease and prompt visiting a memory clinic

Honjo¹,

Takechi

2019

Psychogeriatrics

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Background Early detection and diagnosis is critical in enhancing treatment outcomes for those with cognitive disease. However, most Japanese patients are averse to visiting mental health clinics or taking cognitive screening examinations. A new simple screening test is needed that is acceptable to patients and encourages them to visit a memory clinic if indicated. Methods We developed a brief screening examination, consisting of four common Japanese old stories, for detection of cognitive disease. A total of 311 patients at three outpatient memory clinics completed the screening test, responding to a 10‐question, fill‐in‐the‐blanks assessment. Questions were read aloud to patients with visual impairment, and we transcribed the spoken responses of patients who were physically incapable of writing. The Hasegawa Dementia Scale‐Revised (HDS‐R) and Mini‐Mental State Examination (MMSE) were administered at the same time. Results Using the developed Japanese Old Stories Cognitive Scale (JOSS), we found significant differences between dementia and control or mild cognitive impairment (MCI) groups. The JOSS was less affected by education level than the HDS‐R or MMSE, possibly because Japanese old stories are usually learned from family members during preschool years. The JOSS may be able to detect remote memory disturbance in addition to other cognitive dysfunctions. Conclusions Most patients with AD, even in advanced stages, are averse to visiting a memory clinic because it can be difficult to accept any resulting diagnosis of cognitive disease. JOSS is a quick and simple screening tool to gather evidence of cognitive dysfunction and prompt a referral to a memory clinic. Patients with cognitive disease found the JOSS acceptable, and its high specificity could be useful in encouraging patients to visit already‐crowded memory clinics for formal diagnosis and intervention.

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“…6, left-side column). Such hypersynchronization phenomenon could be attributed to overall neuronal excitatory enhancement 47 , reduced disinhibition of neurons 30 , or as a compensatory mechanism related to brain plasticity changes triggered by AD synaptic and neuronal loss 48,49 .…”

Section: Prospective Neuromarker Importance Of Source Meg-fc Analysismentioning

confidence: 99%

Cluster-permutation statistical analysis for high-dimensional brain-wide functional connectivity mapping

Sánchez-Bornot

López

Bruña

et al. 2019

Preprint

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Brain functional connectivity (FC) analyses based on magnetoencephalographic (MEG) signals have yet to exploit the intrinsic high-dimensional information. Typically, these analyses are constrained to regions of interest to avoid the curse of dimensionality, which leads to conservative hypothesis testing. We removed such constraint by extending cluster-permutation statistics for high-dimensional MEG-FC analyses. We demonstrated the feasibility of this approach by identifying MEG-FC resting-state changes in mild cognitive impairment (MCI), a prodromal stage of Alzheimer’s disease. We found dense clusters of increased connectivity strength in MCI compared to healthy controls (hypersynchronization), in delta (1-4 Hz) and higher-theta (6-8 Hz) bands oscillations. These clusters mainly consisted of interactions between occipitofrontal and occipitotemporal regions in the left hemisphere and could potentially be used as neuromarkers of early progression in Alzheimer’s disease. Our novel approach can be used to generate high-resolution statistical FC maps for neuroimaging studies in general.

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Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse

Cited by 198 publications

References 398 publications

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

Japanese Old Stories Cognitive Scale: a screening test to detect cognitive disease and prompt visiting a memory clinic

Cluster-permutation statistical analysis for high-dimensional brain-wide functional connectivity mapping

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