Alzheimer's Disease

Hyman, Bradley T.; Damasio, H; Damasio, A R; Hoesen, Gary W. Van

doi:10.1146/annurev.pu.10.050189.000555

Cited by 47 publications

(20 citation statements)

References 58 publications

(87 reference statements)

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“…In AD, it appears that procedural memory, or memory used for motor and perceptual skills, is relatively spared until very late stages of the disease [71]. Unchanged levels of COMT and DAT may indicate that recycling of dopamine was not changed in this area and has a limited role in behavioral changes in AD patients.…”

Section: Discussionmentioning

confidence: 99%

Disturbed Neurotransmitter Transporter Expression in Alzheimer’s Disease Brain

Chen

Reese²,

Kim³

et al. 2011

JAD

110

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Alzheimer disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters – glutamate, acetylcholine, dopamine, and serotonin - has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT)) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1–3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase (COMT) was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy.

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Section: Discussionmentioning

confidence: 99%

Disturbed Neurotransmitter Transporter Expression in Alzheimer’s Disease Brain

Chen

Reese²,

Kim³

et al. 2011

JAD

110

View full text Add to dashboard Cite

show abstract

“…Follow ing this massive denervation, the replacement is very rap id with restoration completed within a very short time. This replacement also occurs rapidly in aged animals [30][31][32], AD results in a loss of the lamina II and III EC projec tion neurons, resulting in a significant denervation simi lar to that found in experimental animals, isolating the ipsilateral hippocampus [33]. One major difference be tween AD and experimental animal studies is the time course of the EC cell loss.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of Synaptic Density in the Outer Molecular Layer of the Hippocampal Dentate Gyrus in Alzheimer's Disease

Sparks¹,

Price²

1996

Dement Geriatr Cogn Disord

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We quantified the synaptic density in the outer molecular layer of the hippocampal dentate gyrus. Autopsy material from 9 individuals with Alzheimer disease (AD) were compared to 10 age-matched, postmortem-matched controls without dementia, using standard electron microscopy. Statistical analyses showed a significant change in the density of synapses between controls and AD subjects. There was a significant decline in the width of the entire molecular layer in the AD material. Synaptic density showed a significant correlation with synaptic apposition length in both AD and control groups. As the number of synapses declined, the synaptic apposition length increased. The decline in density of synapses in the AD group might reflect the degree of neuronal loss in the entorhinal cortex. Such a loss in synaptic connectivity could play a key role in memory-related problems associated with AD.

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“…In brain tissue, AD is also associated with changes in signaling cascades (Camandola and Mattson, 2011; Hyman and Yuan, 2012), gene expression (Cooper-Knock et al, 2012; De Jager and Bennett, 2013), reorganization of connectivity (Hyman et al, 1989; Mesulam et al, 2004; Rekart et al, 2004; Rodriguez et al, 2012), synapse loss (Terry et al, 1991; Scheff and Price, 2006; Serrano-Pozzo et al, 2011), synaptic dysfunction (Malinow, 2012; Mucke and Selkoe, 2012) and neuron loss (Morrison and Hof, 2002; Giannakopoulos et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Evidence for Alzheimer’s disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons

et al. 2014

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Alzheimer’s disease (AD) is associated with alterations in the distribution, number, and size of inputs to hippocampal neurons. Some of these changes are thought to be neurodegenerative, whereas others are conceptualized as compensatory, plasticity-like responses, wherein the remaining inputs reactively innervate vulnerable dendritic regions. Here, we provide evidence that the axospinous synapses of human AD cases and mice harboring AD-linked genetic mutations (the 5XFAD line) exhibit both, in the form of synapse loss and compensatory changes in the synapses that remain. Using array tomography, quantitative conventional electron microscopy, immunogold electron microscopy for AMPARs, and whole-cell patch-clamp physiology, we find that hippocampal CA1 pyramidal neurons in transgenic mice are host to an age-related synapse loss in their distal dendrites, and that the remaining synapses express more AMPA-type glutamate receptors. Moreover, the number of axonal boutons that synapse with multiple spines is significantly reduced in the transgenic mice. Through serial section electron microscopic analyses of human hippocampal tissue, we further show that putative compensatory changes in synapse strength are also detectable in axospinous synapses of proximal and distal dendrites in human AD cases, and that their multiple synapse boutons may be more powerful than those in non-cognitively impaired human cases. Such findings are consistent with the notion that the pathophysiology of AD is a multivariate product of both neurodegenerative and neuroplastic processes, which may produce adaptive and/or maladaptive responses in hippocampal synaptic strength and plasticity.

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Alzheimer's Disease

Cited by 47 publications

References 58 publications

Disturbed Neurotransmitter Transporter Expression in Alzheimer’s Disease Brain

Disturbed Neurotransmitter Transporter Expression in Alzheimer’s Disease Brain

Quantitative Assessment of Synaptic Density in the Outer Molecular Layer of the Hippocampal Dentate Gyrus in Alzheimer's Disease

Evidence for Alzheimer’s disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons

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