Lifestyle and Alzheimer’s Disease

Bartolotti, Nancy; Lazarov, Orly

doi:10.1016/b978-0-12-802851-3.00007-3

Cited by 5 publications

(2 citation statements)

References 280 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, elderly people participating in frequent leisure activities expressed a 38% lower risk of developing dementia [ 111 ]. Also, early life linguistic ability is a strong predictor for later-life cognitive performance and being raised in a bilingual family, for example, protects against AD [ 16 , 112 ]. Conversely, the occurrence of a parental death between age 0 and 18 is associated with a higher incidence of AD [ 113 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with a high prevalence among the elderly and a huge personal and societal impact. Recent epidemiological studies have indicated that the incidence and age of onset of sporadic AD can be modified by lifestyle factors such as education, exercise, and (early) stress exposure. Early life adversity is known to promote cognitive decline at a later age and to accelerate aging, which are both primary risk factors for AD. In rodent models, exposure to ‘negative’ or ‘positive’ early life experiences was recently found to modulate various measures of AD neuropathology, such as amyloid-beta levels and cognition at later ages. Although there is emerging interest in understanding whether experiences during early postnatal life also modulate AD risk in humans, the mechanisms and possible substrates underlying these long-lasting effects remain elusive.MethodsWe review literature and discuss the role of early life experiences in determining later age and AD-related processes from a brain and cognitive ‘reserve’ perspective. We focus on rodent studies and the identification of possible early determinants of later AD vulnerability or resilience in relation to early life adversity/enrichment.ResultsPotential substrates and mediators of early life experiences that may influence the development of AD pathology and cognitive decline are: programming of the hypothalamic–pituitary–adrenal axis, priming of the neuroinflammatory response, dendritic and synaptic complexity and function, overall brain plasticity, and proteins such as early growth response protein 1 (EGR1), activity regulated cytoskeleton-associated protein (Arc), and repressor element-1 silencing transcription factor (REST).ConclusionsWe conclude from these rodent studies that the early postnatal period is an important and sensitive phase that influences the vulnerability to develop AD pathology. Yet translational studies are required to investigate whether early life experiences also modify AD development in human studies, and whether similar molecular mediators can be identified in the sensitivity to develop AD in humans.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Alzheimer’s disease (AD), being one of over 40 maladies caused by protein or peptide aggregation and misfolding, is a progressive and multifactorial disease leading to age-related changes in the brain. The etiology of AD is complex and influenced by genetic, environmental, and/or lifestyle factors 1 . In spite of intense research efforts invested into different aspects of this devastating form of dementia, AD is currently still incurable 2 .…”

Section: Introductionmentioning

confidence: 99%

Peptide backbone modifications of amyloid β (1–40) impact fibrillation behavior and neuronal toxicity

Schwarze

Korn

Höfling

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Fibril formation of amyloid β (Aβ) peptides is one of the key molecular events connected to Alzheimer’s disease. The pathway of formation and mechanism of action of Aβ aggregates in biological systems is still object of very active research. To this end, systematic modifications of the Phe19–Leu34 hydrophobic contact, which has been reported in almost all structural studies of Aβ40 fibrils, helps understanding Aβ folding pathways and the underlying free energy landscape of the amyloid formation process. In our approach, a series of Aβ40 peptide variants with two types of backbone modifications, namely incorporation of (i) a methylene or an ethylene spacer group and (ii) a N-methylation at the amide functional group, of the amino acids at positions 19 or 34 was applied. These mutations are expected to challenge the inter-β-strand side chain contacts as well as intermolecular backbone β-sheet hydrogen bridges. Using a multitude of biophysical methods, it is shown that these backbone modifications lead, in most of the cases, to alterations in the fibril formation kinetics, a higher local structural heterogeneity, and a somewhat modified fibril morphology without generally impairing the fibril formation capacity of the peptides. The toxicological profile found for the variants depend on the type and extent of the modification.

show abstract