Neurobiology of Aging最新文献

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0197-4580(25)00090-9","DOIUrl":"10.1016/S0197-4580(25)00090-9","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Page IFC"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in the impact of background noise on neural speech tracking","authors":"Björn Herrmann","doi":"10.1016/j.neurobiolaging.2025.06.001","DOIUrl":"10.1016/j.neurobiolaging.2025.06.001","url":null,"abstract":"<div><div>Tracking the envelope of speech in the brain is important for speech comprehension. Recent research suggests that acoustic background noise can enhance neural speech tracking, enabling the auditory system to robustly encode speech even under unfavorable conditions. Aging and hearing loss are associated with internal, neural noise in the auditory system, raising the question whether additional acoustic background noise enhances neural speech tracking in older adults. In the current electroencephalography study, younger (∼25.5 years) and older adults (∼68.5 years) listened to spoken stories in quiet (clear) or in the presence of background noise at a wide range of different signal-to-noise ratios. In younger adults, early neural speech tracking responses (&lt;0.15 s) were enhanced by minimal background noise, indicating response facilitation through noise. In contrast, older adults, compared to younger adults, showed enhanced neural speech tracking for clear speech and speech masked by minimal background noise, but the acoustic noise led to little enhancement of the early neural tracking response in older people. The data demonstrate different sensitivity of the auditory cortex to speech masked by noise between younger and older adults. The results are consistent with the idea that the auditory cortex of older people exhibits more internal, neural noise that enhances neural speech tracking but that additional acoustic noise does not further support speech encoding. The work points to a highly non-linear auditory system that differs between younger and older adults.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 10-20"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age","authors":"David Villarroel-Campos ,&nbsp;Elena R. Rhymes ,&nbsp;Andrew P. Tosolini ,&nbsp;Bilal Malik ,&nbsp;Alessio Vagnoni ,&nbsp;Giampietro Schiavo ,&nbsp;James N. Sleigh","doi":"10.1016/j.neurobiolaging.2025.05.002","DOIUrl":"10.1016/j.neurobiolaging.2025.05.002","url":null,"abstract":"<div><div>A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological diseases. A decline in this essential process has also been identified in many aging models, perhaps compounding age-related neurodegeneration. Via intravital imaging, we recently determined that, despite a reduction in overall motility, the run speed and displacement of anterograde mitochondrial transport were unexpectedly enhanced in 19–22 month-old mouse peripheral nerves. Here, to determine how aging impacts a different axonal cargo, we evaluated <em>in vivo</em> trafficking of signalling endosomes in motor axons of mouse sciatic nerves from 3 to 22 months. Contrasting with mitochondria, we did not detect alterations in signalling endosome speed, but found a consistent rise in pausing that manifested after 18 months. We then treated muscles with brain-derived neurotrophic factor (BDNF), which regulates axonal transport of signalling endosomes in motor neurons; however, we observed no change in the processivity defect at 22 months, consistent with downregulation of the BDNF receptor TrkB at the neuromuscular junction. Together, these findings indicate that aging negatively impacts signalling endosome trafficking in motor axons, likely through dampened BDNF signalling at the motor neuron-muscle interface.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 1-9"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifiable risk factor profiles moderate the effect of β-amyloid pathology on cognition in aging","authors":"Mohini Bhade ,&nbsp;Stefania Pezzoli ,&nbsp;Joseph Giorgio ,&nbsp;Tyler J. Ward ,&nbsp;Joseph R. Winer ,&nbsp;Theresa M. Harrison ,&nbsp;Susan M. Landau ,&nbsp;William J. Jagust","doi":"10.1016/j.neurobiolaging.2025.05.001","DOIUrl":"10.1016/j.neurobiolaging.2025.05.001","url":null,"abstract":"<div><div>Although modifiable risk factors may account for around 40 % of population variability in dementia risk, the effect of risk factor interrelationships on pathology-cognition relationships is poorly understood. Using risk factor data from a cohort of 203 cognitively normal older adults (73 ± 6.4 years, 56 % female), we used k-means clustering to assign participants to one of three risk-related profiles; namely, positive-active (physical/cognitive activity, education), positive-affective (sleep, depression, personality), and negative multi-domain clusters. Linear mixed-effects models showed an attenuated effect of β-amyloid on non-memory cognition decline in positive profiles (positive-active: β=3.7, p = 0.008, positive-affective: β=3.7, p = 0.007) compared to the negative profile. While a significant entorhinal tau x time effect (p &lt; 0.001) was observed in a model predicting episodic memory decline, cluster membership did not modify this relationship. These findings suggest that different risk profiles moderate pathology-cognition relationships, and highlight the role of groups of modifiable resilience factors in mitigating the effects of β-amyloid deposition.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Pages 54-63"},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0197-4580(25)00081-8","DOIUrl":"10.1016/S0197-4580(25)00081-8","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Page IFC"},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal relationships among cerebrospinal fluid biomarkers, cerebral blood flow, and grey matter volume in individuals with a familial history of Alzheimer's disease","authors":"Safa Sanami ,&nbsp;Brittany Intzandt ,&nbsp;Julia Huck ,&nbsp;Sylvia Villeneuve ,&nbsp;Yasser Iturria-Medina ,&nbsp;Claudine J. Gauthier ,&nbsp;Prevent-AD research group","doi":"10.1016/j.neurobiolaging.2025.04.011","DOIUrl":"10.1016/j.neurobiolaging.2025.04.011","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a complex disease that involves complex interactions between protein biomarkers such as amyloid beta (Aβ) and tau, neurodegeneration, cerebrovascular health and inflammation. However, how these factors interact, especially in the early phases of disease development remain unclear. To address this, this study analyzed four-year longitudinal data from 110 cognitively unimpaired older adults with a family history of AD in the PreventAD cohort. We investigated relationships between CSF Aβ, 181-phosphorylated tau (p-tau), interleukin-8 (IL-8), cerebral blood flow (CBF), and grey matter volume (GMV) in groups with high and low cardiovascular risk levels. Longitudinally, lower CSF Aβ within participants (a proxy for higher brain amyloid) was linked to a slower decline in regional CBF, particularly in those with higher cardiovascular risk. Similarly, in the high vascular risk group, higher IL-8 at baseline was associated with greater decline in CBF in the right superior temporal gyrus. Further, lower baseline CBF was associated with greater CSF p-tau accumulation over time. Finally, higher baseline CSF p-tau was associated with faster GM atrophy over 4 years, particularly in the hippocampus. Our results highlight the complex interactions between CSF misfolded proteins, inflammatory markers, and brain regional CBF and atrophy, and how these effects are more pronounced in individuals with higher vascular risk factor load. These findings demonstrate the need for comprehensive models of AD pathophysiology that integrate vascular health and inflammation measures alongside traditional biomarkers.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Pages 43-53"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower locus coeruleus integrity is associated with diminished practice effects in clinically unimpaired older individuals","authors":"Lindsay F. Smegal ,&nbsp;Marion Baillet ,&nbsp;Christoph Schneider ,&nbsp;Roos J. Jutten ,&nbsp;Rory Boyle ,&nbsp;Dorene M. Rentz ,&nbsp;Keith A. Johnson ,&nbsp;Reisa A. Sperling ,&nbsp;Kathryn V. Papp ,&nbsp;Heidi I.L. Jacobs","doi":"10.1016/j.neurobiolaging.2025.03.015","DOIUrl":"10.1016/j.neurobiolaging.2025.03.015","url":null,"abstract":"<div><div>The locus coeruleus (LC), one of the earliest structures affected by tau pathology in Alzheimer’s disease (AD), plays an important role in modulating arousal and learning. In asymptomatic early stages of AD, more sensitive measures to identify subtle cognitive changes are needed. Previous studies indicate that practice effects can signal initial AD-related learning deficits. Here, we assessed the association between LC integrity and practice effects. We combined dedicated LC-MRI methods with at-home computerized face-name letter task (FNLT), a Mnemonic Similarity Task (MST), and a one card learning task (OCL) performed monthly over one year in 76 older participants from the Harvard Aging Brain Study. Higher LC integrity was related to lower MST reaction times at baseline, and lower MST and FNLT reaction times over one year. No significant associations were found with the OCL. Participants with low accuracy practice effect trajectories exhibited low baseline PACC-5 scores, whereas those with higher reaction times over time displayed low LC integrity, high entorhinal, and high amygdala tau at baseline. These findings suggest reaction times measured monthly may be a sensitive measure for early AD-related biomarkers such as LC integrity and tau burden in preclinical AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Pages 13-24"},"PeriodicalIF":3.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presenilin 1 hemizygosity has no overt deleterious phenotypic outcomes in sheep: Potential implications for therapeutic targets in Alzheimer's disease","authors":"Natasha E. Mckean ,&nbsp;Jun Liu ,&nbsp;Skye R. Rudiger ,&nbsp;Jennifer M. Kelly ,&nbsp;Clive McLaughlan ,&nbsp;Paul J. Verma ,&nbsp;John Hardy ,&nbsp;James F. Gusella ,&nbsp;Henrik Zetterberg ,&nbsp;Suzanne J. Reid ,&nbsp;Renee H. Handley ,&nbsp;Klaus Lehnert ,&nbsp;Greg T. Sutherland ,&nbsp;Amanda Heslegrave ,&nbsp;Elena Veleva ,&nbsp;Rhiannon Laban ,&nbsp;John F. Pearson ,&nbsp;Simon C. Bawden ,&nbsp;Russell G. Snell","doi":"10.1016/j.neurobiolaging.2025.04.006","DOIUrl":"10.1016/j.neurobiolaging.2025.04.006","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative condition and one of the most significant medical challenges today. Dominant mutations causing early-onset AD have been identified in the presenilin 1 and 2 (<em>PSEN1</em> and <em>PSEN2</em>), and the amyloid precursor protein (<em>APP</em>) genes. Either PSEN1 or PSEN2 is required by γ-secretase, a functional complex that cleaves APP to produce amyloid-beta (Aβ) peptides of varying lengths. These mutations result in relative or absolute increases in the longer Aβ peptides (Aβ_1–40, Aβ _1–42), which accumulate as plaques, characteristic of both early and late-onset AD. To investigate the effects of modulating PSEN1 expression, we have produced <em>PSEN1</em> hemizygous sheep. Sheep <em>PSEN</em> and <em>APP</em> genes are highly conserved relative to humans, including the APP proteolytic cleavage sites, and like humans, sheep naturally develop plaques and TAU tangles with age. At five years of age, the <em>PSEN1</em> hemizygous animals are phenotypically and biochemically normal. Interestingly, the characteristic Aβ peptide levels in their cerebrospinal fluid and plasma remain at wildtype levels, indicating that a 50 % reduction in PSEN1 abundance does not materially affect γ-secretase’s APP cleavage activity. These results suggest that generalized regulation of <em>PSEN1</em> expression is unlikely to be an effective therapeutic approach for AD on its own. However, it does suggest that loss of one <em>PSEN1</em> allele may be tolerated in higher organisms, with no deleterious side-effects. It is therefore possible that knocking-out or knocking-down one copy of <em>PSEN1</em> via genetic modification will be tolerated in humans, especially as functional hemizygous humans are present in the population (gnomad). These kinds of therapies could potentially prevent AD caused by dominant gain-of-function mutations in <em>PSEN1</em>.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Pages 25-33"},"PeriodicalIF":3.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theta-gamma transcranial alternating current stimulation enhances ballistic motor performance in healthy young and older adults","authors":"Nishadi N. Gamage ,&nbsp;Wei-Yeh Liao ,&nbsp;Brodie J. Hand ,&nbsp;Philip J. Atherton ,&nbsp;Mathew Piasecki ,&nbsp;George M. Opie ,&nbsp;John G. Semmler","doi":"10.1016/j.neurobiolaging.2025.04.010","DOIUrl":"10.1016/j.neurobiolaging.2025.04.010","url":null,"abstract":"<div><div>Theta-gamma transcranial alternating current stimulation (TG tACS) over primary motor cortex (M1) can improve ballistic motor performance in young adults, but the effect on older adults is unknown. This study investigated the effects of TG tACS on motor performance and M1 excitability in 18 young and 18 older adults. High-definition TG tACS (6 Hz theta, 75 Hz gamma) or sham tACS was applied over right M1 for 20 min during a ballistic left-thumb abduction motor training task performed in two experimental sessions. Motor performance was quantified as changes in movement acceleration during and up to 60 min after training. Transcranial magnetic stimulation (TMS) was used to assess changes in M1 excitability with motor-evoked potentials (MEP) and short-interval intracortical inhibition (SICI) before and after training. We found that TG tACS increased motor performance compared with sham tACS in young and older adults (<em>P</em> &lt; 0.001), with greater effects for young adults (<em>P</em> = 0.01). The improved motor performance with TG tACS lasted at least 60 min after training in both age groups. Motor training was accompanied by greater MEP amplitudes with TG tACS compared to sham tACS in young and older adults (<em>P</em> &lt; 0.001), but SICI did not vary between tACS sessions (<em>P</em> = 0.40). These findings indicate that TG tACS over M1 improves motor performance and alters training-induced changes in M1 excitability in healthy young and older adults. TG tACS may therefore be beneficial to alleviate motor deficits in the ageing population.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"152 ","pages":"Pages 1-12"},"PeriodicalIF":3.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calpain and caspase regulate Aβ peptide production via cleavage of KINDLIN2 encoded by the AD-associated gene FERMT2","authors":"Chloé Najdek ,&nbsp;Pauline Walle ,&nbsp;Amandine Flaig,&nbsp;Anne-Marie Ayral,&nbsp;Florie Demiautte,&nbsp;Audrey Coulon,&nbsp;Valérie Buiche,&nbsp;Neuro-CEB Brain Bank,&nbsp;Erwan Lambert ,&nbsp;Philippe Amouyel,&nbsp;Carla Gelle,&nbsp;Dolores Siedlecki-Wullich,&nbsp;Julie Dumont,&nbsp;Devrim Kilinc,&nbsp;Fanny Eysert ,&nbsp;Jean-Charles Lambert,&nbsp;Julien Chapuis","doi":"10.1016/j.neurobiolaging.2025.04.009","DOIUrl":"10.1016/j.neurobiolaging.2025.04.009","url":null,"abstract":"<div><div>The adapter protein KINDLIN2, encoded by the Alzheimer's disease (AD) genetic risk factor <em>FERMT2</em>, was identified as a modulator of APP processing. KINDLIN2 directly interacts with APP to modulate its metabolism, and KINDLIN2 underexpression impairs long-term potentiation in an APP-dependent manner. Altogether, these data suggest that loss of KINDLIN2 could have a detrimental effect on synaptic function and promote AD pathophysiological process. In this study, we identified KINDLIN2 as a novel substrate of caspases and calpain I, two well-characterized cysteine proteases involved in the regulation of synaptic plasticity. These cleavages resulted in the dissociation of the F0 and F1 domains of KINDLIN2 that are necessary for it to function as an adapter protein. Furthermore, we demonstrate that these cleavages lead to a decrease in KINDLIN2’s ability to control APP processing. Overall, these KINDLIN2 cleavages appear as potential new mechanisms in the regulation of KINDLIN2 functions at the synapse and could be of interest for the pathophysiology of AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 117-125"},"PeriodicalIF":3.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}