Abstract：
:Damaged mitochondria may be one of the earliest manifestations of Alzheimer's disease. Because oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in Alzheimer's disease. Here we used a recently developed positron emission tomography (PET) probe targeting mitochondrial complex I (MC-I), 18F-BCPP-EF, to non-invasively visualize mitochondrial abnormalities in the brains of tau transgenic mice (rTg4510). Tauopathy and neuroinflammation were visualized by PET using a tau probe 11C-PBB3 and a translocator protein probe, 18F-FEBMP, respectively. A marked reduction in 18F-BCPP-EF uptake was observed in hippocampal and forebrain regions of tau transgenic mice, colocalizing with regions of tauopathy, neuronal damage, and neuroinflammation. MC-I signals were highly correlated with atrophy assayed by magnetic resonance imaging, but negatively associated with inflammatory signals, indicating that neuronal metabolic signals measured by MC-I PET were robust to inflammatory interference. MC-I may be a useful imaging biomarker to detect neuronal damage and metabolic changes with minimal interference from concomitant glial hypermetabolism.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Barron AM,Ji B,Fujinaga M,Zhang MR,Suhara T,Sahara N,Aoki I,Tsukada H,Higuchi Mdoi
10.1016/j.neurobiolaging.2020.05.003subject
Has Abstractpub_date
2020-10-01 00:00:00pages
140-148eissn
0197-4580issn
1558-1497pii
S0197-4580(20)30155-Xjournal_volume
94pub_type
杂志文章abstract：:To determine if the membrane disordering effect of ethanol on cerebral microvessels is altered with age, the steady state fluorescence polarization (P) of diphenyl-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) which report on the membrane core and surface region, respectively, ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90005-v
更新日期：1993-05-01 00:00:00
abstract：:The central biochemical pathology of anorexia and the natural aging of the brain is similar. Biochemical models for drug withdrawal and depression may also assist in understanding geriatric anorexia. Norepinephrine, corticotropin releasing factor and beta-endorphin may key neurotransmitters in all of these conditions....
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(88)80010-1
更新日期：1988-01-01 00:00:00
abstract：: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 bra...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.07.001
更新日期：2018-11-01 00:00:00
abstract：:In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)97327-d
更新日期：1995-05-01 00:00:00
abstract：:Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.10.016
更新日期：2013-04-01 00:00:00
abstract：PURPOSE:The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. METHODS:16 C, 6 CI, and 7 D subjects of comparable age w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00130-6
更新日期：2003-07-01 00:00:00
abstract：:Amnestic mild cognitive impairment (aMCI) is accompanied by the accelerated cognitive decline and rapid brain degeneration with aging. However, the age-related alterations of the topological organization of the brain connectome in aMCI patients remained largely unknown. In this study, we constructed the brain structur...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.08.005
更新日期：2017-11-01 00:00:00
abstract：:An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challeng...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.008
更新日期：2016-10-01 00:00:00
abstract：:The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(96)00208-4
更新日期：1997-01-01 00:00:00
abstract：:Alzheimer's disease (AD) is generally considered to be a disorder primarily affecting memory. It is increasingly recognized that the clinical presentation or "cognitive phenotype" is variable. The apolipoprotein E ε4 (APOE ε4) allele has been associated with an amnestic presentation, but does not appear to fully expla...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.11.003
更新日期：2012-07-01 00:00:00
abstract：:Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that el...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/s0197-4580(03)00032-0
更新日期：2003-11-01 00:00:00
abstract：:The goal of this experiment was to determine the correlations among different behavioral and neurobiological measures in aged rats. Aged Sprague-Dawley rats were given a battery of cognitive and sensorimotor tests, followed by electrophysiological assessment of sleep and biochemical measurements of various neurotransm...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(89)80008-9
更新日期：1989-01-01 00:00:00
abstract：:In an autopsy series of 19 individuals, age-ranged 24-94, a relatively age-spared region, the anterior-ventral thalamus, was analyzed by immunohistochemical techniques to visualize neurons (neurofilament protein), astrocytes (glial fibrillary acidic protein), microglial cells (CD68) and amyloid precursor protein. The ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.12.015
更新日期：2008-06-01 00:00:00
abstract：:Although peripheral nerves are capable of regeneration, advanced age decreases the potential for functional recovery after injury. The cellular mechanisms for this are not currently understood. Here, we performed sciatic nerve grafting with young (2 months old) and aged (18 months old) Brown-Norway male rats, in which...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.05.004
更新日期：2016-09-01 00:00:00
abstract：:Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease that resembles early-onset frontotemporal dementia with bone lesions called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with Alzheimer's...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.12.008
更新日期：2018-04-01 00:00:00
abstract：:Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.04.004
更新日期：2016-10-01 00:00:00
abstract：:After a decade of intense study of cholinergic therapies for Alzheimer's disease, three conditions in this field are apparent: 1) The potential that cholinergic agents will ameliorate the memory dysfunction of Alzheimer patients (as 1-dopa benefits Parkinson patients) is still a stimulus for research. 2) Cholinergic n...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(89)80017-x
更新日期：1989-01-01 00:00:00
abstract：:Apolipoprotein E (ApoE) ε4 is known as a genetic risk factor for Alzheimer's disease (AD). This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). F...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.020
更新日期：2012-10-01 00:00:00
abstract：:Behavioral profiles of young (3-6 months) and aged (24-27 months) rats were compared in three respects: (1) short-term memory, (2) exploration and (3) locomotor activity. Compared to young rats, aged rats were impaired in the 8-arm radial maze acquisition, but not in the delayed reinforced alternation acquisition. The...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(87)90033-9
更新日期：1987-09-01 00:00:00
abstract：:It has been suggested that the A beta fragment of the amyloid precursor protein in Alzheimer's disease arises from internal translation initiation at Met596 (1). Here we use the recently described in vitro model of A beta production and secretion (2) to examine this hypothesis. We show that A beta is no longer detecta...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90041-9
更新日期：1993-11-01 00:00:00
abstract：:Aged rats show decrements in performance on cognitive tasks that require the use of spatial learning and memory. We used the 8-arm radial water maze (RAWM) to measure spatial learning as a function of age in young (6 months) and old (21 months) male F344 rats. Rats were placed in the RAWM in different start arms with ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(03)00041-1
更新日期：2004-02-01 00:00:00
abstract：:We recently, characterized a novel peptide of the egg-laying controlling caudodorsal cells (CDC) of Lymnaea stagnalis. Here, we show that the novel peptide has autoinhibitory actions and its expression is significantly up-regulated in reproductively senescent animals. Intracellular recordings show that when bath-appli...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.020
更新日期：2006-05-01 00:00:00
abstract：:Calcium-binding proteins play potentially important roles in neurogenesis and neuroprotective mechanism(s). Some evidence exists that brain calbindin-D28K (CALB) is regulated by androgens. In the present study, calretinin (CALRET) and CALB patterns were determined by Western analysis in the medial basal hypothalamus (...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00060-8
更新日期：1998-05-01 00:00:00
abstract：:Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they associate with cholesterol concentrations and, for rs6084, coronary artery disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent e...
journal_title：Neurobiology of aging
pub_type： 杂志文章,多中心研究
doi：10.1016/j.neurobiolaging.2006.11.015
更新日期：2008-05-01 00:00:00
abstract：:We have shown previously that the TG-3 and MPM-2 antibodies recognize phosphoepitopes common to mitosis and degenerating neurons of Alzheimer's disease(AD) brain. Here, we have evaluated their occurrence in human brain biopsy tissue, and confirm that they are absent in mature neurons of adult brain, but reappear durin...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00071-2
更新日期：1998-07-01 00:00:00
abstract：:Energy deficiency and dysfunction of the Na,K-ATPase are common consequences of many pathological insults. Glutamate through cyclic GMP and cyclic GMP-dependent protein kinase (PKG) has been shown to stimulate alpha(2/3)-Na,K-ATPase activity in the central nervous system. Thus, a slight impairment of this pathway may ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.08.013
更新日期：2005-06-01 00:00:00
abstract：:The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.021
更新日期：2016-10-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.011
更新日期：2015-03-01 00:00:00
abstract：:Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample con...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.02.014
更新日期：2019-06-01 00:00:00
abstract：:To characterize the mechanisms underlying region- and age-dependent hippocampal synaptic dysfunction in Alzheimer's disease, we used transgenic CRND8 mice, expressing the Swedish-Indiana APP mutation. In 2-month-old mice, no β-amyloid plaques deposition, but the presence of soluble oligomers, were found in CA1 area bu...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.002
更新日期：2015-01-01 00:00:00
