Brain‐derived neurotrophic factor and neurotrophin‐3 levels in Alzheimer's disease brains

Durany, Núria; Michel, Tanya; Jellinger, K.; Cruz-Sánchez, F. F.; Cervós-Navarro, J.; Riederer, Peter

doi:10.1016/s0736-5748(00)00046-0

Cited by 139 publications

(94 citation statements)

References 30 publications

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“…The correspondence of relatively greater activation in multiple right hemisphere regions with equivalent behavioral memory performances supports the notion of compensation through the employment of more bilateral network regions (see network view in Cabeza [9]). In all, support for the compensatory hypothesis has been demonstrated across a whole host of neuropsychological [2,10,27,41] and neuroimaging [3,4,6,22] investigations, as well as with neurochemical [13,17,35], neurotrophic [18], and mitochondrial DNA alterations [33].…”

Section: Resultsmentioning

confidence: 92%

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Han

Houston

Jak

et al. 2007

Neurobiology of Aging

139

114

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Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE ε4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-ε4 and 12 ε4 subjects. The ε4 group displayed greater activation than the non-ε4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE ε4-related deficiencies associated with verbal episodic memory encoding and consolidation.

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Section: Resultsmentioning

confidence: 92%

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Han

Houston

Jak

et al. 2007

Neurobiology of Aging

139

114

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show abstract

“…40-42 It may be that, after an initial decline in memory proficiency following damage to MTL structures, patients in the preclinical stage of AD are able to effectively recruit compensatory brain resources (e.g., frontal and temporal cortical regions important for executive functions and semantic memory) to halt or slow further memory decline for a period of time. A similar compensatory response in certain brain-derived neurotrophic factors 43,44 or cholinergic activity 45 may also attenuate memory changes for a time. Given that adequate cholinergic activity and neurotrophic mechanisms are partly responsible for the maintenance of neuronal function and structural integrity, these findings suggest that, under conditions of progressive neurodegeneration, the MTL stimulates the overexpression of certain cholinergic and neurotrophic factors as a possible mechanism of compensation.…”

Section: Discussionmentioning

confidence: 99%

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease

Bondi¹,

Houston²,

Eyler³

et al. 2005

Neurology

340

292

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Objective-To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults.Methods-Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE ε4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions.Results-Nondemented older adults with an APOE ε4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched ε3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. Conclusions-The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE ε4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.Studies of nondemented older adults who later develop Alzheimer disease (AD) show a subtle decline in episodic memory prior to emergence of the obvious cognitive and behavioral changes required for a clinical diagnosis of the disease. 1-7 Often this decline in episodic memory is evident some years prior to the development of dementia and has been shown to predict the subsequent development of AD. [1][2][3][4]8,9 In addition, the ε4 allele of the gene coding for APOE is linked to an increased risk of developing late-onset AD. 10,11 There have been a variety of brain changes associated with the APOE ε4 allele in AD, including structural 12,13 and functional brain changes, 14 as well as subtle neuropsychologic deficits. 8,9,15 Further, studies suggest that the pathologic burden of AD may begin decades-not years-prior to the diagnosis of AD and may be influenced by one's APOE genotype. 16Given the increasing emergence of treatments for dementia, sensitive and reliable markers of incipient dementia are needed to enhance our ability to detect AD in its earliest stages when potential neuroprotective agents might be most effective. 17 fMRI offers considerable promise as a noninvasive technique for detection of early brain changes associated with an incipient Initial work 19 demonstrated an increase in the intensity and extent of brain activation in nondemented middle-aged and older adults with the APOE ε4 allele during verbal learning, suggesting a compensatory mechanism wherein APOE ε4 carriers util...

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“…With only one notable exception (Durany et al, 2000), decreased BDNF levels were reported (Phillips et al, 1991;Murray et al, 1994;Connor et al, 1997;Ferrer et al, 1999;Hock et al, 2000;Holsinger et al, 2000;Michalski and Fahnestock, 2003). In all studies reporting decreased BDNF levels, however, late stages of AD were studied in which considerable neuron loss has already occurred (Braak and Braak, 1991;Hof et al, 1999).…”

Section: Changes Of Bdnf Expression In Admentioning

confidence: 99%

Induction of Brain-Derived Neurotrophic Factor in Plaque-Associated Glial Cells of Aged APP23 Transgenic Mice

Burbach¹,

Hellweg²,

Haas³

et al. 2004

J. Neurosci.

116

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Brain-derived neurotrophic factor (BDNF) is a versatile neurotrophic factor that has been implicated in cell survival, cell differentiation, axonal growth, and activity-dependent synaptic plasticity. Changes in BDNF expression have also been reported during the course of several neurological disorders, including Alzheimer's disease (AD). The role of BDNF in AD, however, has remained elusive. To learn more about this neurotrophic factor, we investigated BDNF expression in brain of amyloid precursor protein overexpressing mice (APP23 transgenic mice). In situ hybridization revealed BDNF mRNA signals associated with amyloid plaques. Laser microdissection in combination with quantitative RT-PCR demonstrated a sixfold increase of BDNF mRNA in the immediate plaque vicinity, a threefold increase in a tissue ring surrounding the plaque, and control levels in interplaque areas comparable with those measured in age-matched nontransgenic mice. Double immunofluorescence localized BDNF to microglial cells and astrocytes surrounding the plaque. Cortical BDNF protein levels were quantified by ELISA demonstrating a Ͼ10-fold increase compared with age-matched controls. This upregulation of BDNF protein significantly correlated with the ␤-amyloid load in the transgenic animals. Taken together, our data demonstrate a plaque-associated upregulation of BDNF in APP23 transgenic mice and implicate this neurotrophin in the regulation of inflammatory and axonal growth processes in the plaque vicinity.

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Brain‐derived neurotrophic factor and neurotrophin‐3 levels in Alzheimer's disease brains

Cited by 139 publications

References 30 publications

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease

Induction of Brain-Derived Neurotrophic Factor in Plaque-Associated Glial Cells of Aged APP23 Transgenic Mice

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