Is synaptic loss a unique hallmark of Alzheimer's disease?

Scheff, Stephen W.; Neltner, Janna H.; Nelson, Peter T.

doi:10.1016/j.bcp.2013.12.028

Cited by 108 publications

(104 citation statements)

References 164 publications

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“…The involvement of those pathological hallmarks tends to correlate antemortem cognitive status as well as synapse loss in multiple drain areas [65]. The role of TDP-43 in neuronal function has not been researched in AD models, and whether abnormal TDP-43 perturbs neuronal function in AD is currently unknown.…”

Section: The Role Of Tdp-43 In Neuronal Dysfunctionmentioning

confidence: 99%

The Role of TDP-43 in Alzheimer’s Disease

Chang

Tan

et al. 2015

Mol Neurobiol

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The transactive response DNA binding protein (TDP-43) has long been characterized as a main hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U, also known as FTLD-TDP). Several studies have indicated TDP-43 deposits in Alzheimer's disease (AD) brains and have robust connection with AD clinical phenotype. FTLD-U, which was symptomatically connected with AD, may be predictable for the comprehension of the role TDP-43 in AD. TDP-43 may contribute to AD through both β-amyloid (Aβ)-dependent and Aβ-independent pathways. In this article, we summarize the latest studies concerning the role of TDP-43 in AD and explore TDP-43 modulation as a potential therapeutic strategy for AD. However, to date, little of pieces of the research on TDP-43 have been performed to investigate the role in AD; more investigations need to be confirmed in the future.

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Section: The Role Of Tdp-43 In Neuronal Dysfunctionmentioning

confidence: 99%

The Role of TDP-43 in Alzheimer’s Disease

Chang

Tan

et al. 2015

Mol Neurobiol

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“…On the other hand, change in cognition associates better with the accumulation of NFTs [4]. It is becoming more evident that the loss of synapses and synaptic function is a prominent feature of AD that synaptic loss in the cortex and hippocampus is an early event that associates strongly with cognitive dysfunction (see reviews [9, 10]), although synaptic loss is not unique to this type of dementia [11]. …”

Section: Introductionmentioning

confidence: 99%

Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease

Price

Ansari

Roberts

et al. 2014

JAD

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132

102

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Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer’s disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [3H]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with mini mental status examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequela associated with AD.

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“…Synaptic pathology plays a central role in Alzheimer's disease (AD) [1,2] and correlates with cognitive decline [3][4][5][6]. Because "synaptic failure" is increasingly being recognized as a core feature of AD pathophysiology [7], synaptic proteins hold promise to serve as novel candidate markers of neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study

Lista¹,

Toschi

Baldacci

et al. 2017

JAD

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Abstract. We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35) S. Lista et al. / CSF Neurogranin in Neurodegenerative Diseasescognitively HC (n = 23)]. CSF neurogranin concentrations were significantly higher in AD patients compared with both HC subjects and FTD patients, suggesting that increased CSF neurogranin concentrations may indicate AD-related pathophysiology. CSF neurogranin was independently associated with both total tau and hyperphosphorylated tau proteins, whereas a non-significant correlation with the 42-amino acid-long amyloid-␤ peptide was evident. CSF neurogranin, however, was not superior to core AD biomarkers in differentiating HC from the three diagnostic groups, and it did not improve their diagnostic accuracy. We conclude that further classification and longitudinal studies are required to shed more light into the potential role of neurogranin as a pathophysiological biomarker of neurodegenerative diseases.

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Is synaptic loss a unique hallmark of Alzheimer's disease?

Cited by 108 publications

References 164 publications

The Role of TDP-43 in Alzheimer’s Disease

The Role of TDP-43 in Alzheimer’s Disease

Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease

Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study

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