Vulnerability and resilience to Alzheimer’s disease: early life conditions modulate neuropathology and determine cognitive reserve

Lesuis, Sylvie L.; Hoeijmakers, Lianne; Kőrösi, Anikó; Rooij, Susanne R. de; Swaab, D.F.; Kessels, Helmut W.; Lucassen, Paul J.; Krugers, Harm J.

doi:10.1186/s13195-018-0422-7

Cited by 90 publications

(86 citation statements)

References 240 publications

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“…The correlation between PAL performance and age is supported by existing literature showing an age-dependent decline in episodic memory and by studies using CANTAB PAL both within, and independently of, the TwinsUK cohort [61][62][63] . Increased education also showed significant effects on cognition but despite recent studies, it remains unclear whether this is due to cognitive reserve or a confounding effect of higher cognitive abilities increasing the likelihood of further education [64][65][66][67] .…”

Section: Discussionmentioning

confidence: 98%

Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence

et al. 2020

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Aging induces cellular and molecular changes including modification of stem cell pools. In particular, alterations in aging neural stem cells (NSCs) are linked to age-related cognitive decline which can be modulated by lifestyle. Nutrient-sensing pathways provide a molecular basis for the link between lifestyle and cognitive decline. Adopting a back-translation strategy using stem cell biology to inform epidemiological analyses, here we show associations between cellular readouts of NSC maintenance and expression levels of nutrient-sensing genes following NSC exposure to aging human serum as well as morphological and gene expression alterations following repeated passaging. Epidemiological analyses on the identified genes showed associations between polymorphisms in SIRT1 and ABTB1 and cognitive performance as well as interactions between SIRT1 genotype and physical activity and between GRB10 genotype and adherence to a Mediterranean diet. Our study contributes to the understanding of neural stem cell molecular mechanisms underlying human cognitive aging and hints at lifestyle modifiable factors.

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Section: Discussionmentioning

confidence: 98%

Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence

et al. 2020

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“…Some of the downstream targets that we tested, such as neurogenesis and the number of ectopic cells, may be of relevance for learning and memory performance. Indeed, it has been reported that ELS protocols impair various behavioural domains, including memory; incidentally, ELS effects are generally much more prominent in male than in female rodents, which is one of the reasons why we restricted the present study to male mice only. Likewise, HT‐induced seizures affect memory performance later in life, although the results so far were somewhat equivocal .…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia‐induced seizures followed by repetitive stress are associated with age‐dependent changes in specific aspects of the mouse stress system

Umeoka

Robinson

Turimella

et al. 2019

J Neuroendocrinology

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Stress is among the most frequently self-reported factors provoking epileptic seizures in children and adults. It is still unclear, however, why some people display stress-sensitive seizures and others do not. Recently, we showed that young epilepsy patients with stress-sensitive seizures exhibit a dysregulated hypothalamic-pituitaryadrenal (HPA)-axis. Most likely, this dysregulation gradually develops, and is triggered by stressors occurring early in life (early-life stress [ELS]). ELS may be particularly impactful when overlapping with the period of epileptogenesis. To examine this in a controlled and prospective manner, the present study investigated the effect of repetitive variable stressors or control treatment between postnatal day (PND) 12 and 24 in male mice exposed on PND10 to hyperthermia (HT)-induced prolonged seizures (control: normothermia). A number of peripheral and central indices of HPAaxis activity were evaluated at pre-adolescent and young adult age (ie, at PND25 and 90, respectively). At PND25 but not at PND90, body weight gain and absolute as well as relative (to body weight) thymus weight were reduced by ELS (vs control), whereas relative adrenal weight was enhanced, confirming the effectiveness of the stress treatment. Basal and stress-induced corticosterone levels were unaffected, though, by ELS at both ages. HT by itself did not affect any of these peripheral markers of HPA-axis activity, nor did it interact with ELS. However, centrally we did observe age-specific interaction effects of HT and ELS with regard to hippocampal glucocorticoid receptor mRNA expression, neurogenesis with the immature neurone marker doublecortin and the number of hilar (ectopic) granule cells using Prox1 staining. This 2 of 15 | UMEOKA Et Al. | INTRODUC TI ONApproximately 50% of all children and adults with epilepsy acknowledge stress as a seizure-provoking factor, 1,2 ranking stress among the most frequently self-reported precipitants of seizures. 2-10 Why some individuals show stress-sensitivity in seizure activity and others do not still remains unclear. One explanation could be that the former as opposed to the latter group responds differently to stress as, for example, reflected by aberrant hypothalamic-pituitary-adrenal (HPA) activation or downstream targets after stress. In accordance, recent evidence obtained in a cohort of children and adolescents (6-17 years of age) with epilepsy indicated that those with stress-sensitive compared to individuals with stress-insensitive seizures or healthy controls show a blunted cortisol response to experimentally induced stress. 11Possibly, this renders hormonal negative-feedback actions on the brain less adequate, which could result in increased levels of proexcitatory central stress hormones such as corticotrophin-releasing hormone. 12 Which elements of the stress system become aberrant at specific developmental stages is not easy to investigate in humans with stress-sensitive seizures because this would require prospective longitudinal investigation of both centr...

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“…Early-life stress (ES) has been associated with cognitive deficits in adulthood [1][2][3][4] and there is emerging evidence that ES also increases the risk for developing Alzheimer's disease (AD) [5,6]. For example, among children who have experienced physical neglect, mild cognitive impairment, considered a prodromal phase of AD, is more frequently observed [7].…”

Section: Introductionmentioning

confidence: 99%

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

Abbink¹,

Kotah²,

Hoeijmakers³

et al. 2020

Preprint

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Background Early-life stress (ES) is an emerging risk factor for later-life development of Alzheimer’s disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice, and how these relate to the previously reported amyloid pathology and microglial profile. Methods We induced ES by limiting nesting and bedding material from postnatal days (P) 2-9. We studied in WT mice (at P9, P30 and 6 months) and in APP/PS1 mice (at 4 and 10 months) i) GFAP coverage, cell density and complexity in hippocampus (HPC) and entorhinal cortex (EC); ii) hippocampal gene expression of astrocyte markers; and iii) the relationship between astrocyte, microglia and amyloid markers. Results In WT mice, ES increased GFAP coverage in HPC subregions at P9, and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age. Conclusions Our data suggest that ES leads to alterations to the astrocytic response to amyloid-β pathology.

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Vulnerability and resilience to Alzheimer’s disease: early life conditions modulate neuropathology and determine cognitive reserve

Cited by 90 publications

References 240 publications

Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence

Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence

Hyperthermia‐induced seizures followed by repetitive stress are associated with age‐dependent changes in specific aspects of the mouse stress system

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

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