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Neurobiology of Aging

Adam D Richard, Xin-Li Tian, Madison W El-Saadi, Xiao-Hong Lu
Cognitive decline is a feature of aging. Accumulating evidence suggests that the brain extracellular matrix (ECM) is involved in the process of aging-dependent cognitive impairment and neurodegeneration by regulating synaptic neurotransmission and affecting neuroplasticity. Age-related changes in brain structure and cognition are not uniform across the whole brain. Being one of the most vulnerable brain regions to aging-dependent alterations, striatum is integral to several central nervous system functions, such as motor, cognition, and affective control...
July 23, 2018: Neurobiology of Aging
Olga Pletnikova, Yusuke Kageyama, Gay Rudow, Katherine D LaClair, Marilyn Albert, Barbara J Crain, Jing Tian, David Fowler, Juan C Troncoso
Sporadic Alzheimer's disease (AD) usually presents clinically after 65 years of age, but its pathological changes begin decades earlier. We examined for AD pathology in the postmortem brains of 431 of subjects aged 30-65 years not clinically characterized. Among 40-49 year olds, 15% showed diffuse amyloid β (Aβ) plaques, with a prevalence of 80% in ApoE4/E4, 42% in E4/E3, and <1% in E3/E3 subjects. Aβ deposits appeared after age 49 years in subjects with E3/E3 genotypes. Neuritic plaques first appeared after age 50 years and increased steadily with age in all genotypes...
July 19, 2018: Neurobiology of Aging
Walter Gulisano, Marcello Melone, Domenica D Li Puma, Maria Rosaria Tropea, Agostino Palmeri, Ottavio Arancio, Claudio Grassi, Fiorenzo Conti, Daniela Puzzo
The increase of oligomeric amyloid-beta (oAβ) has been related to synaptic dysfunction, thought to be the earliest event in Alzheimer's disease pathophysiology. Conversely, the suppression of endogenous Aβ impaired synaptic plasticity and memory, suggesting that the peptide is needed in the healthy brain. However, different species, aggregation forms and concentrations of Aβ might differently influence synaptic function/dysfunction. Here, we have tested the contribution of monomeric and oligomeric Aβ42 and Aβ40 at 200 nM and 200 pM concentrations on hippocampal long-term potentiation and spatial memory...
July 18, 2018: Neurobiology of Aging
Adith Mohan, Anbupalam Thalamuthu, Karen A Mather, Yiru Zhang, Vibeke S Catts, Cynthia Shannon Weickert, Perminder S Sachdev
Altered inhibition-excitation balance is implicated in brain aging. We hypothesized that expression of 14 genes encoding proteins localized to synapses or interneurons would show age-related changes relative to 1 another in postmortem tissue from the prefrontal cortex of 37 individuals (18-78 years) and that synaptic or interneuron markers would be differentially correlated with human brain volumes across aging. The majority of genes examined were differentially expressed with age, most being downregulated...
July 18, 2018: Neurobiology of Aging
Elisabeth J Vinke, Marius de Groot, Vikram Venkatraghavan, Stefan Klein, Wiro J Niessen, M Arfan Ikram, Meike W Vernooij
With aging, the brain undergoes several structural changes. These changes reflect the normal aging process and are therefore not necessarily pathologic. In fact, better understanding of these normal changes is an important cornerstone to also disentangle pathologic changes. Several studies have investigated normal brain aging, both cross-sectional and longitudinal, and focused on a broad range of magnetic resonance imaging (MRI) markers. This study aims to comprise the different aspects in brain aging, by performing a comprehensive longitudinal assessment of brain aging, providing trajectories of volumetric (global and lobar; subcortical and cortical), microstructural, and focal (presence of microbleeds, lacunar or cortical infarcts) brain imaging markers in aging and the sequence in which these markers change in aging...
July 17, 2018: Neurobiology of Aging
Andreana Benitez, Jens H Jensen, Maria Fatima Falangola, Paul J Nietert, Joseph A Helpern
Myelin breakdown and neural fiber loss occur in aging. This study used white matter tract integrity metrics derived from biophysical modeling using Diffusional Kurtosis Imaging to assess loss of myelin (i.e., extraaxonal diffusivity, radial direction, De,⊥ ) and axonal density (i.e., axonal water fraction) in cognitively unimpaired older adults. Tract-based spatial statistics and region of interest analyses sought to identify ontogenic differences and age-related changes in white matter tracts using cross-sectional and longitudinal data analyzed with general linear and mixed-effects models...
July 17, 2018: Neurobiology of Aging
Dennis Chan, Meredith Shafto, Rogier Kievit, Fiona Matthews, Molly Spink, Michael Valenzuela, Rik N Henson
This study tested the hypothesis that mid-life intellectual, physical, and social activities contribute to cognitive reserve (CR). Two hundred five individuals (196 with magnetic resonance imaging) aged 66-88 years from the Cambridge Centre for Ageing and Neuroscience ( were studied, with cognitive ability and structural brain health measured as fluid IQ and total gray matter volume, respectively. Mid-life activities (MAs) were measured using the Lifetime of Experiences Questionnaire. Multivariable linear regression found that MAs made a unique contribution to late-life cognitive ability independent of education, occupation, and late-life activities...
July 16, 2018: Neurobiology of Aging
Alexandre Bourgeois, Inger Lauritzen, Thomas Lorivel, Charlotte Bauer, Frédéric Checler, Raphaëlle Pardossi-Piquard
The triple transgenic mouse model (3×TgAD: APPswe, TauP301L , PS1M146V ) recapitulates both amyloid β (Aβ)- and tau-related lesions as well as synaptic and memory deficits. In these mice, we reported an early apathy-like behavior and alterations in synaptic plasticity appearing concomitantly with intraneuronal accumulation of C99 in the subiculum. To delineate the genuine contribution of C99 on the above phenotypes, we generated double transgenic mice (2×TgAD: APPswe, TauP301L ) that accumulate C99 without Aβ deposition or hyperphosphorylation of tau and compared them to 3×TgAD mice...
July 12, 2018: Neurobiology of Aging
Niklas Mattsson, Oscar Eriksson, Olof Lindberg, Michael Schöll, Björn Lampinen, Markus Nilsson, Philip S Insel, Ronald Lautner, Olof Strandberg, Danielle van Westen, Henrik Zetterberg, Kaj Blennow, Sebastian Palmqvist, Erik Stomrud, Oskar Hansson
Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ, tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure...
July 11, 2018: Neurobiology of Aging
Alaina M Reagan, Xiaowu Gu, Sijalu Paudel, Nicole M Ashpole, Michelle Zalles, William E Sonntag, Zoltan Ungvari, Anna Csiszar, Laura Otalora, Willard M Freeman, Michael B Stout, Michael H Elliott
Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles...
July 10, 2018: Neurobiology of Aging
Pei-Chien Tsai, Yi-Chu Liao, Kang-Yang Jih, Bing-Wen Soong, Kon-Ping Lin, Yi-Chung Lee
Mutations in the annexin A11 gene (ANXA11) have been recently identified in British patients and Italian patients with amyotrophic lateral sclerosis (ALS), and their role in other ALS populations remains unclear. The aim of this study was to investigate the ANXA11 mutations in a Taiwanese ALS cohort. Mutational analysis of ANXA11 was performed in 286 unrelated Taiwanese patients with ALS by Sanger sequencing. Eight ANXA11 missense variants were identified initially, and only one of them was absent from population databases...
July 10, 2018: Neurobiology of Aging
Carla Centeno, Diogo Medeiros, Mikkel Malling Beck, Liav Lugassy, David Fernandez Gonzalez, Jean Francois Nepveu, Marc Roig
We investigated whether cortico-spinal excitability (CSE), a marker of synaptic plasticity, is associated with age-related differences in the consolidation of motor memory. Young and older participants practiced a visuomotor tracking task. Skill retention was assessed 8 and 24 hours after motor practice. Transcranial magnetic stimulation applied over the primary motor cortex at rest and during an isometric muscle contraction was used to assess absolute and normalized to baseline CSE at different points after practice...
July 4, 2018: Neurobiology of Aging
Jin-Ru Zhang, Hong Jin, Kai Li, Cheng-Jie Mao, Ya-Ping Yang, Fen Wang, Chen-Chen Gu, Hui-Jun Zhang, Jing Chen, Chun-Feng Liu
Mutations in Leucine-rich repeat kinase 2 (LRRK2) are recognized as the most frequent genetic factors contributing to Parkinson's disease (PD). The aim of our study was to explore LRRK2 variants in PD patients within the mainland Han Chinese population. The whole coding regions of LRRK2 from 296 PD patients were sequenced by targeted regions sequencing and exome sequencing. Eighteen rare variants were identified in 27 PD patients, and 13 of them (M100T, L153W, A459S, S722N, R792K, C925Y, R981K, S1007T, V1447M, R1677S, N2308D, N2313S, and S2350I) were firstly reported in PD...
July 4, 2018: Neurobiology of Aging
Katarzyna Gaweda-Walerych, Emilia J Sitek, Ewa Narożańska, Michalina Wezyk, Bogna Brockhuis, Cezary Zekanowski, Jarosław Sławek
Loss-of-function mutations in progranulin (PGRN) gene cause frontotemporal lobar degeneration. Here, we report a case of a 63-year-old woman with a 2-year history of speech impairment, diagnosed with a nonfluent variant of primary progressive aphasia, a subtype of frontotemporal lobar degeneration. In this patient, a novel heterozygous frameshift mutation, c.77delG, in exon 2 of PGRN gene, introducing premature stop codon, p.(C26SfsX28), has been identified. Cultured fibroblasts derived from the patient and her asymptomatic first-degree relative with c...
July 2, 2018: Neurobiology of Aging
Bouchra Ouled Amar Bencheikh, Etienne Leveille, Jennifer A Ruskey, Dan Spiegelman, Christopher Liong, Edward A Fon, Guy A Rouleau, Yves Dauvilliers, Nicolas Dupre, Roy N Alcalay, Ziv Gan-Or
Saposin C (SapC), encoded by PSAP, is required for the activity of glucocerebrosidase, encoded by GBA. Although GBA mutations have been studied thoroughly in Parkinson disease (PD), genetic studies on SapC are still lacking. PSAP was sequenced in 1123 PD patients and 1153 controls, and data from additional 1167 patients and 1685 controls were examined. A total of 6 patients had SapC mutations in the 2 combined cohorts, but no statistically significant association after correction for multiple comparisons was found...
July 2, 2018: Neurobiology of Aging
Liisa A M Galea, Meighen M Roes, Christina J Dimech, Carmen Chow, Rand Mahmoud, Stephanie E Lieblich, Paula Duarte-Guterman
Menopause is associated with cognitive decline, and hormone therapies (HTs) may improve cognition depending on type and timing of HTs. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin 6 months later, and all rats were trained in the Morris water maze...
June 30, 2018: Neurobiology of Aging
Eun-Joo Kim, Young-Eun Kim, Ja-Hyun Jang, Eun-Hae Cho, Duk L Na, Sang Won Seo, Na-Yeon Jung, Jee H Jeong, Jay C Kwon, Kee Hyung Park, Kyung Won Park, Jae-Hong Lee, Jee Hoon Roh, Hee-Jin Kim, Soo Jin Yoon, Seong Hye Choi, Jae-Won Jang, Chang-Seok Ki, Seung Hyun Kim
To identify pathogenic variants in 107 Korean patients with sporadic frontotemporal dementia (FTD), 46 genes related to FTD, amyotrophic lateral sclerosis, and other dementias were screened by next-generation sequencing. Hexanucleotide repeats in C9orf72 gene were also tested by repeat-primed polymerase chain reaction. Next-generation sequencing revealed one known pathogenic variant (c.708+1G>A) in the GRN gene in a patient with behavioral variant FTD (bvFTD). In addition, a novel in-frame deletion (c.2675_2683del) in the CSF1R gene was identified in a patient with bvFTD who had severe bifrontal atrophy with frontal subcortical white matter changes...
June 30, 2018: Neurobiology of Aging
Ilse M J Kant, Jeroen de Bresser, Simone J T van Montfort, Ellen Aarts, Jorrit-Jan Verlaan, Norman Zacharias, Georg Winterer, Claudia Spies, Arjen J C Slooter, Jeroen Hendrikse
Physical frailty is an age-associated syndrome of decreased reserve leading to vulnerability to physiological stressors and associated with negative outcomes. The underlying structural brain abnormalities of physical frailty are unclear. We investigated the association between brain volume, cortical brain infarcts, and physical frailty. In this multicenter study, 214 nondemented participants were classified as frail (n = 32), prefrail (n = 107), or nonfrail (n = 75) based on the Fried frailty phenotype. The associations between frailty and brain volumes and cortical brain infarcts were investigated by linear or logistic regression analyses...
June 30, 2018: Neurobiology of Aging
Stefanie Lerche, Gerrit Machetanz, Benjamin Roeben, Isabel Wurster, Milan Zimmermann, Anna-Katharina von Thaler, Inga Liepelt-Scarfone, Gerhard W Eschweiler, Andreas Fallgatter, Florian Metzger, Walter Maetzler, Daniela Berg, Kathrin Brockmann
REM sleep behavior disorder (RBD) represents a major and relatively specific prodromal marker for synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies, and multisystem atrophy. Because PD patients primarily suffer from executive dysfunction, we hypothesized that individuals with RBD show an impairment in the nonamnestic executive domain rather than in amnestic domains. To address this question, we investigated a cohort of 1145 healthy elderly (183 with RBD) cross-sectionally and a subgroup of 544 of them longitudinally (144 with RBD) over 6 years...
June 30, 2018: Neurobiology of Aging
Abbi R Hernandez, Jordan E Reasor, Leah M Truckenbrod, Keila T Campos, Quinten P Federico, Kaeli E Fertal, Katelyn N Lubke, Sarah A Johnson, Benjamin J Clark, Andrew P Maurer, Sara N Burke
The link between age-related cellular changes within brain regions and larger scale neuronal ensemble dynamics critical for cognition has not been fully elucidated. The present study measured neuron activity within medial prefrontal cortex (PFC), perirhinal cortex (PER), and hippocampal subregion CA1 of young and aged rats by labeling expression of the immediate-early gene Arc. The proportion of cells expressing Arc was quantified at baseline and after a behavior that requires these regions. In addition, PER and CA1 projection neurons to PFC were identified with retrograde labeling...
June 30, 2018: Neurobiology of Aging
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