Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

Akram, Afia Muhammad; Christoffel, Daniel J.; Rocher, Anne B.; Bouras, Constantin; Kovari, Eniko Veronika; Perl, Daniel P.; Morrison, John H.; Herrmann, Françoís; Haroutunian, Vahram; Giannakopoulos, Pantéleimon; Hof, Patrick R.

doi:10.1016/j.neurobiolaging.2007.03.007

Cited by 75 publications

(55 citation statements)

References 85 publications

(130 reference statements)

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“…Thus, dendritic spine loss in the PreC occurs incrementally across clinical diagnostic categories, a conclusion supported by our observation of a significant association between lower PreC dendritic spines and worsened performance on the neuropsychological tests relevant to PreC function (e.g., episodic memory, MMSE). These correlations in the PreC are similar to observations in the prefrontal cortex (PFC), where total numbers of spinophilin-ir dendritic spines correlated significantly with lower MMSE scores (Akram et al, 2008). However, in contrast to our study, Akram et al, reported a correlation of PFC spinophilin-ir spine measures with Braak staging for NFTs, but not with Aβ deposition.…”

Section: Discussionsupporting

confidence: 82%

Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease

Abrahamson

Ryu

et al. 2017

Neurobiology of Aging

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Precuneus (PreC) cortex is affected with amyloid plaques early in Alzheimer’s disease (AD), and this pathology may be associated with alterations in PreC synapses and cognitive impairment. We quantified the spinophilin-immunoreactive (ir) dendritic spine density and the intensity of spinophilin immunofluorescence, the latter as a measure of relative protein levels of spinophilin, in PreC lamina III from 33 subjects with clinical diagnoses of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild-moderate AD (mAD), or severe AD (sAD). Both measures of spinophilin were lower in mAD and sAD compared with NCI. The MCI group had higher protein levels of spinophilin compared with mAD and sAD, and higher spinophilin-ir dendritic spine density compared with sAD. Lower spinophilin-ir dendritic spine density and relative protein levels of spinophilin were associated with greater amyloid beta (Aβ) plaque burden, detected with a derivative of Pittsburgh compound-B (6-CN-PiB), and worse cognitive performance. Clinical onset of AD is marked by the loss of PreC spinophilin-ir dendritic spines that is related to Aβ pathology and may contribute to cognitive symptoms early in the disease.

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Section: Discussionsupporting

confidence: 82%

Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease

Abrahamson

Ryu

et al. 2017

Neurobiology of Aging

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“…It is also possible that AD causes a loss of GR-positive neurons which contributes to aberrant responses to increased corticosterone compared to WT controls. Indeed, the CA1 region, site of GR expression, is an area of considerable cell loss in AD (Mueller 2010; Akram 2008). …”

Section: Discussionmentioning

confidence: 99%

3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

Rothman

Herdener

Camandola

et al. 2012

Neurobiology of Aging

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Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling.

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“…As the increase in SIPB-to-neuron ratio was only apparent between 10-month-old mice and 6-month-old mice rather than 6-month-old mice and 2-month-old mice, compensatory synaptic remodeling may only have been activated after substantial neurodegeneration. Similar observations have been observed for synaptophysin and other presynaptic proteins in neocortical association areas at Braak stage III of AD progression, prior to neurofibrillary pathology [42], for drebrin in the prefrontal cortex of patients with mild cognitive impairment followed by 40–60% decrease in severe AD [43], as well as for glutamatergic presynaptic bouton density in midfrontal gyrus of mild cognitive impairment patients [44], but not for total numbers of spinophilin-immunoreactive puncta in the CA1 and CA3 fields of hippocampus and area 9 in elderly individuals with various degrees of cognitive decline [45]. Moreover, Bronfman et al [46] described a “synaptic sprouting compensatory mechanism” in the hippocampus of aged PDAPP mice exhibiting atrophied cholinergic neurons in the medial septum.…”

Section: Discussionmentioning

confidence: 99%

Region-specific neuron and synapse loss in the hippocampus of APPSL/PS1 knock-in mice

Brasnjevic¹,

Lardenoije

Schmitz

et al. 2013

Translational Neuroscience

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Transgenic mouse models with knock-in (KI) expression of human mutant amyloid precursor protein (APP) and/or human presenilin 1 (PS1) may be helpful to elucidate the cellular consequences of APP and PS1 misprocessing in the aging brain. Age-related alterations in total numbers of neurons and in numbers of synaptophysin-immunoreactive presynaptic boutons (SIPB), as well as the amyloid plaque load were analyzed in the hippocampal dentate gyrus (DG), CA3, and CA1–2 of 2- and 10-month-old APPSL/PS1 homozygous KI, APPSL (expressing human mutant APP751 carrying the Swedish [K670N/M671L] and London [V717I] mutations under Thy-1 promoter), and PS1 homozygous KI mice (expressing human PS1 mutations [M233T and L235P]). APPSL/PS1 homozygous KI mice, but neither APPSL mice nor PS1 homozygous KI mice, showed substantial age-related loss of neurons (−47.2%) and SIPB (−22.6%), specifically in CA1–2. PS1 homozygous KI mice showed an age-related increase in hippocampal granule cell numbers (+37.9%). Loss of neurons and SIPB greatly exceeded the amount of local extracellular Aβ aggregation and astrocytes, whereas region-specific accumulation of intraneuronal Aβ preceded neuron and synapse loss. An age-related increase in the ratio of SIPB to neuron numbers in CA1–2 of APPSL/PS1 homozygous KI mice was suggestive of compensatory synaptic plasticity. These findings indicate a region-selectivity in intra- and extraneuronal Aβ accumulation in connection with neuron and synapse loss in the hippocampus of APPSL/PS1 homozygous KI mice.

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Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

Cited by 75 publications

References 85 publications

Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease

Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease

3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

Region-specific neuron and synapse loss in the hippocampus of APPSL/PS1 knock-in mice

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