The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The size of the postsynaptic density is correlated with the number of presynaptic vesicles, the number of postsynaptic receptors and the ready-releasable pool of transmitter.

“In turn, the size of the postsynaptic density is correlated with the number of presynaptic vesicles, the number of postsynaptic receptors and the ready-releasable pool of transmitter (Harris and Stevens, 1989; Nusser et al., 1998; Schikorski and Stevens, 1999, 2001; Arellano et al., 2007a).”

• cites Harris and Stevens, 1989 sourcePartly supported

  The Serial electron microscopy section reports that PSD area is proportional to the number of vesicles in the presynaptic axonal varicosity. The Relationships between hippocampal spine geometry and synaptic efficacy section infers that larger PSDs likely contain more receptors, but does not count them. Neither section establishes a correlation with the readily releasable transmitter pool. Page numbers are not available in the indexed passages. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Nusser et al., 1998 sourcePartly supported

  The Figure 4 description reports a positive correlation between synapse size and AMPA-receptor immunolabeling in hippocampal synapses. The paper does not establish that postsynaptic density size correlates with presynaptic vesicle number or the readily releasable transmitter pool; its introductory mention of pool size concerns variability, not that correlation. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Schikorski and Stevens, 1999, 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Previous studies in animal models of Alzheimer's disease have shown that amyloid-β plaques induce local morphological alterations to the dendrites in contact with amyloid-β.

“Previous studies in animal models of Alzheimer’s disease have shown that amyloid-β plaques induce local morphological alterations to the dendrites in contact with amyloid-β (Tsai et al., 2004; Spires et al., 2005; Knafo et al., 2009a, b; Merino-Serrais et al., 2011).”

• cites Tsai et al., 2004 sourceNot checked — no full text of the source
• cites Spires et al., 2005 sourceSupported
• cites Knafo et al., 2009a, bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Abnormal phosphorylation of tau leads to the formation of paired helical filaments (PHFs), the main components of intraneuronal neurofibrillary tangles.

“In the brain, abnormal phosphorylation of the microtubule-associated protein tau leads to the formation of paired helical filaments (PHFs), the main components of intraneuronal neurofibrillary tangles (Grundke-Iqbal et al., 1986).”

• cites Grundke-Iqbal et al., 1986 sourcePartly supported

  The Abstract says the findings suggest that abnormally phosphorylated tau is a component of paired helical filaments (PHFs), and identifies neurofibrillary tangles as a major location of PHFs. It does not establish the stronger causal claim that abnormal phosphorylation leads to PHF formation. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The length of the spine neck is proportional to the extent of biochemical and electrical isolation of the spine from its parent dendrite.

“Moreover, the length of the spine neck is proportional to the extent of biochemical and electrical isolation of the spine from its parent dendrite (Majewska et al., 2000a, b; Araya et al., 2006).”

• cites Majewska et al., 2000a, bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Araya et al., 2006 sourcePartly supported

  The opening section (page unavailable) says biochemical compartmentalization occurs at spine heads because the neck creates a diffusional bottleneck. It also reports that electrical attenuation increases with neck length. It does not establish that the extent of biochemical isolation is proportional to neck length. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Spine head volume is correlated with the area of the postsynaptic density.

“whereas the spine head volume is correlated with the area of the postsynaptic density.”

• cites Harris and Stevens, 1989 sourceSupported
• cites Nusser et al., 1998 sourceCould not verify

  The Figure 2 caption describes a large synapse on a spine and other synapses on smaller spines, but does not establish a correlation between spine-head volume and postsynaptic-density area. Searches for that correlation and for spine volume versus synaptic area found no passage in our copy that states it; page numbers were unavailable. (LLM, conf=0.70)

  Experimental — accuracy not yet measured
• cites Schikorski and Stevens, 1999, 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Pyramidal cells in different cortical regions have considerably distinct structures and the data obtained in one region cannot necessarily be applied to another.

“Second, pyramidal cells in different cortical regions have considerably distinct structures (Elston et al., 2001; Jacobs et al., 2001) and the data obtained in one region cannot necessarily be applied to another.”

• cites Elston et al., 2001 sourceSupported
• cites Jacobs et al., 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The course such diseases take is highly variable as the neuropathological changes are not homogenous, neither among patients nor in different regions of the brain of the same patient, giving rise to variation in the alterations to cortical circuits.

“In addition, the course such diseases take is highly variable as the neuropathological changes are not homogenous, neither among patients nor in different regions of the brain of the same patient, giving rise to variation in the alterations to cortical circuits (Garcia-Marin et al., 2009; Blazquez-Llorca et al., 2010).”

• cites Garcia-Marin et al., 2009 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Blazquez-Llorca et al., 2010Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Studies on the European ground squirrel demonstrated that PHF-like phosphorylation is induced in the brain during hibernation.

“Studies on the European ground squirrel demonstrated that PHF-like phosphorylation is induced in the brain during the hibernation of these animals (Arendt et al., 2003), which is similar to the characteristic increase in tau phosphorylation (Avila et al., 2004).”

• cites Arendt et al., 2003 sourceSupported

May combine two claims.

The volume of the dendritic spine head is related to the size of the postsynaptic density, the number of presynaptic vesicles, and the number of vesicles adjacent to the presynaptic cleft.

“Additionally, the volume of the dendritic spine head is related to the size of the postsynaptic density (Harris and Stevens, 1989; Schikorski and Stevens, 1997; Arellano et al., 2007b), the number of presynaptic vesicles, and the number of vesicles adjacent to the presynaptic cleft (Harris and Stevens, 1989).”

• cites Harris and Stevens, 1989 sourcePartly supported

  The Serial electron microscopy section reports that spine head volume correlates with postsynaptic density area and with the total number of vesicles in the presynaptic axonal varicosity. It says all vesicles in those varicosities were counted, but does not report a separate relationship for vesicles adjacent to the synaptic cleft. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Schikorski and Stevens, 1997 sourceCould not verify

  The Analysis section says the authors measured spine-head volumes and PSD areas, but does not report a relationship between them. Figure 3 (Appendix; page unavailable) reports a correlation between active-zone size and PSD size instead. The presynaptic-vesicle clauses are cited to Harris and Stevens (1989), not to this paper. (LLM, conf=0.72)

  Experimental — accuracy not yet measured
• cites Arellano et al., 2007bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The proximal and distal segments of basal dendrites have different characteristics with respect to integration and synaptic plasticity.

“Moreover, the proximal and distal segments of basal dendrites have different characteristics with respect to integration and synaptic plasticity (Markram et al., 1997; Hausser and Mel, 2003; Gordon et al., 2006; Gelfo et al., 2009; Branco and Häusser, 2011).”

• cites Markram et al., 1997 sourceNot checked — no full text of the source
• cites Hausser and Mel, 2003 sourceNot checked — no full text of the source
• cites Gordon et al., 2006 sourceSupported

Classified as probably not a substantial claim. May combine two claims.

At the cellular level, abnormal tau phosphorylation and the formation of tangles are major events in neuronal degeneration in Alzheimer's disease.

“At the cellular level, abnormal tau phosphorylation and the formation of tangles are major events in neuronal degeneration in Alzheimer’s disease (Grundke-Iqbal et al., 1986).”

• cites Grundke-Iqbal et al., 1986 sourcePartly supported

  The Abstract (p. 4913) identifies neurofibrillary tangles in Alzheimer disease brain and suggests that tau in paired-helical filaments is abnormally phosphorylated. It does not establish that tangle formation and tau phosphorylation are major events in neuronal degeneration. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

PHF-tauAT8 mostly labels the initial stages of a neurofibrillar pathology, while PHF-tauPHF-1 recognizes the later stages.

“Indeed, the vast majority of PHF-tauPHF-1-ir neurons had a large amount of aggregated tau, consistent with the hypothesis that PHF-tauAT8 mostly labels the initial stages of a neurofibrillar pathology, while PHF-tauPHF-1 recognizes the later stages (Blazquez-Llorca et al., 2011).”

• cites Blazquez-Llorca et al., 2011 sourceSupported

May combine two claims.

Neurofibrillary tangles appear to be toxic since they are associated with impaired axonal transport, which provokes cell death.

“However, neurofibrillary tangles appear to be toxic since they are associated with impaired axonal transport, which provokes cell death (Stamer et al., 2002; Terwel et al., 2002; Cente et al., 2006; Smith et al., 2007).”

• cites Stamer et al., 2002 sourcePartly supported

  The Discussion (page not provided) links elevated tau to impaired intracellular transport and suggests that resulting traffic jams may speed degeneration. It does not show that neurofibrillary tangles cause the transport defect or that the defect provokes cell death; it notes transport defects even when tau aggregates are absent or minor. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Terwel et al., 2002 sourceNot checked — no full text of the source
• cites Cente et al., 2006 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

This interpretation is supported by a large number of researchers who study dendritic spine alterations both in humans and animal models.

“This interpretation is also supported by a large number of researchers who study dendritic spine alterations both in humans and animal models (see Penzes et al., 2011; Spires-Jones and Knafo, 2012 for recent reviews).”

• cites Penzes et al., 2011 sourceSupported
• cites Spires-Jones and Knafo, 2012 sourceSupported

May combine two claims.

In the CA1 region, the total neuron density was 15,786 in Patient P9, 11,916 in Patient P13 and 12,193 in Patient P14 (neurons/mm3), and the percentage of phospho-tau neurons varied between these patients.

“In the CA1 region, the total neuron density was 15 786 in Patient P9, 11 916 in Patient P13 and 12 193 in Patient P14 (neurons/mm3), and the percentage of phospho-tau neurons varied between these patients (Fig. 2 and Supplementary material).”

May combine two claims.

In the parahippocampal cortex from Patient P9, all the Lucifer yellow-injected neurons analysed that were PHF-tau+ were considered to be Pattern I, whereas in the CA1 from Patients P9, P13 and P14, all the Lucifer yellow-injected neurons analysed that were PHF-tau+ were Pattern IIa.

“In the parahippocampal cortex from Patient P9, all the Lucifer yellow-injected neurons analysed that were PHF-tau+ were considered to be Pattern I, whereas in the CA1 from Patients P9, P13 and P14, all the Lucifer yellow-injected neurons analysed that were PHF-tau+ were Pattern IIa.”

May combine two claims.

There were significant differences in the frequency distribution of the volume of dendritic spines for all cases, whereby small dendritic spines were more frequent in PHF-tau+ neurons than in PHF-tau− neurons.

“However, there were significant differences in the frequency distribution of the volume of dendritic spines for all cases, whereby small dendritic spines were more frequent in PHF-tau+ neurons than in PHF-tau− neurons (Fig. 8L, O and R).”

May combine two claims.

In Patient P9, the total neuron density in the parahippocampal cortex was 19,560 neurons/mm3, whereas the density of PHF-tauAT8-ir and PHF-tauPHF-1-ir neurons was 2917 and 499 neurons/mm3, respectively (15% and 2.5% of the total neuronal density).

“In Patient P9, the total neuron density in the parahippocampal cortex was 19 560 neurons/mm3, whereas the density of PHF-tauAT8-ir and PHF-tauPHF-1-ir neurons was 2917 and 499 neurons/mm3, respectively (Fig. 2), 15% and 2.5% of the total neuronal density, respectively.”

May combine two claims.

All Lucifer yellow-injected neurons that were PHF-tauAT8-ir were also PHF-tauPHF-1, whereas some Lucifer yellow-injected neurons that were non-immunostained for PHF-tauAT8 were also labelled for PHF-tauPHF-1.

“All Lucifer yellow-injected neurons that were PHF-tauAT8-ir were also PHF-tauPHF-1, whereas some Lucifer yellow-injected neurons that were non-immunostained for PHF-tauAT8 were also labelled for PHF-tauPHF-1 (Supplementary Fig. 5).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Pattern II was subdivided into Patterns IIa (intermediate/advanced stages) and IIb (extreme stage) depending on the extent of neurofibrillary tangle development.

“In the present study, we further subdivided Pattern II into Patterns IIa and IIb, depending on the extent of neurofibrillary tangle development visualized with PHF-tauAT8, PHF-tauPHF-1 and thioflavin S (Pattern IIa, intermediate/advanced stages; Pattern IIb, extreme stage: Fig. 3).”

May combine two claims.

The average dendritic spine length decreased significantly in Patient P9 (14%), whereas no differences were found in Patients P13 and P14.

“The average dendritic spine length decreased significantly in Patient P9 (14%, Fig. 8B), whereas no differences were found in Patients P13 and P14 (Fig. 8E and H; Supplementary Table 2).”

May combine two claims.

The frequency distribution revealed a higher frequency of shorter dendritic spines in PHF-tau+ neurons from Patients P9 and P13, whereas in Patient P14 short dendritic spines were less frequent on PHF-tau+ neurons than PHF-tau− neurons.

“The frequency distribution revealed a higher frequency of shorter dendritic spines in PHF-tau+ neurons from Patients P9 and P13 (Fig. 8C and F), whereas in Patient P14 short dendritic spines were less frequent on PHF-tau+ neurons than PHF-tau− neurons (Fig. 8I).”

May combine two claims.

In Patients P13 and P14, there were statistical differences between PHF-tau− and PHF-tau+ neurons in the medial/distal portions of dendritic spine density, and similar results were found when the data are presented as the average.

“By contrast, in Patients P13 and P14 we found statistical differences between PHF-tau− and PHF-tau+ neurons in the medial/distal portions (Fig. 7C and E), and similar results were found when the data are presented as the average (Fig. 7D and F; Supplementary Table 2).”

May combine two claims.

PHF-tau+ neurons that had well developed neurofibrillary tangles (Pattern IIb) had a reduced dendritic arbor and few or virtually no dendritic spines; the dendritic diameter was also remarkably thin in all these cases.

“However, when PHF-tau+ neurons that had well developed neurofibrillary tangles (Pattern IIb) were injected, these neurons had a reduced dendritic arbor and few or virtually no dendritic spines. The dendritic diameter was also remarkably thin in all these cases (Fig. 6).”

May combine two claims.

Our results indicate that neurons with advanced neurofibrillary tangles display a remarkable loss of dendritic spines, which is consistent with other studies.

“Our results indicate that neurons with advanced neurofibrillary tangles display a remarkable loss of dendritic spines, which is consistent with other studies.”

May combine two claims.

The density of CA3 neurons in Patient P9 was 14,350 neurons/mm3, whereas there were only 8916 neurons/mm3 and 8447 neurons/mm3 in Patients P13 and P14, respectively.

“Importantly, the density of CA3 neurons in Patient P9 was 14 350 neurons/mm3, whereas there were only 8916 neurons/mm3 and 8447 neurons/mm3 in Patients P13 and P14, respectively (Supplementary material), suggesting that the CA3 region in the latter two patients is more pathologically affected than that of Patient P9.”

May combine two claims.

No changes were found in the number, length or volume of dendritic spines in neurons with Pattern I, nor in dendrite diameter.

“As summarized in Fig. 9, no changes were found in the number, length or volume of the dendritic spines in neurons with Pattern I, nor in dendrite diameter, whereas several significant alterations were found in neurons showing Pattern II.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Dendritic spines on pyramidal cells are the main postsynaptic target of excitatory synapses in the cerebral cortex.

“The dendritic spines on pyramidal cells are the main postsynaptic target of excitatory synapses in the cerebral cortex and thus, pyramidal cells are considered the principal building blocks of this structure (DeFelipe and Fariñas, 1992).”

• cites DeFelipe and Fariñas, 1992 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Both PHF-tauAT8 and PHF-tauPHF-1 antibodies were produced in mouse; thus the labeling of neurons for both PHF-tauAT8 and PHF-tauPHF-1 could be due to antibody cross-reactivity.

“Nevertheless, it is important to mention that both PHF-tauAT8 and PHF-tauPHF-1 antibodies were produced in mouse. Thus, the labeling of neurons for both PHF-tauAT8 PHF-tauPHF-1 could be due to antibody cross-reactivity.”

May combine two claims.

Intracellular injections of marker substances in fixed brain tissue is currently considered the best approach to visualize the dendritic spines in the human brain and is a well-established technique.

“Another method involving intracellular injections of marker substances in fixed brain tissue is currently considered the best approach to visualize the dendritic spines in the human brain and is a well-established technique (Einstein, 1988; Buhl et al., 1990).”

• cites Einstein, 1988 sourceNot checked — no full text of the source
• cites Buhl et al., 1990Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

This result is suggestive of a local toxic effect, since the density of dendritic spines in the pre-terminal dendritic segment was similar to that found in dendrites lacking PHF-tauAT8.

“This result is suggestive of a local toxic effect, since the density of dendritic spines in the pre-terminal dendritic segment was similar to that found in dendrites lacking PHF-tauAT8.”

May combine two claims.

It is not possible to know which neurons have developed a neurofibrillar pathology before injection and hence the proportion of cells showing a neurofibrillar pathology is rather unpredictable.

“In addition, it is not possible to know which neurons have developed a neurofibrillar pathology before injection and hence, the proportion of cells showing a neurofibrillar pathology is rather unpredictable.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The morphological alterations observed in human pathological tissue are very difficult to interpret due to the high interindividual variability (sex, age, medical treatment, etc.), factors that could affect brain structure.

“Third, the morphological alterations observed in human pathological tissue are very difficult to interpret due to the high interindividual variability (sex, age, medical treatment, etc.), factors that could affect brain structure.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Pattern II neurons typically form neurofibrillary tangles (tangle stage).

“Neurons with Pattern II typically form neurofibrillary tangles (tangle stage).”

• cites Blazquez-Llorca et al., 2010Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The small dendritic tree, thin dendrites, and very few or no spines in Pattern IIb neurons may simply be due to a more advanced stage of atrophy.

“Finally, Lucifer yellow-injected neurons with Pattern IIb (with well-developed neurofibrillary tangles) had a relatively small dendritic tree, with thin dendrites and very few or no spines, which may simply be due to a more advanced stage of atrophy.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Changes in the denervation/reinnervation of CA3 pyramidal neurons by mossy fibres were found during hibernation/arousal and were associated with a reversible PHF-like phosphorylation of tau over a similar time course.

“Furthermore, changes in the denervation/reinnervation of CA3 pyramidal neurons by mossy fibres were also found during hibernation/arousal (Popov and Bocharova, 1992) and they were associated with a reversible PHF-like phosphorylation of tau over a similar time course.”

• cites Popov and Bocharova, 1992 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Synaptic connections of axons that arise within the same cortical column in the neocortex preferentially innervate the proximal basal dendrites of pyramidal cells.

“For example, the synaptic connections of axons that arise within the same cortical column in the neocortex preferentially innervate the proximal basal dendrites of pyramidal cells (Markram et al., 1997; Feldmeyer et al., 2002).”

• cites Markram et al., 1997 sourceNot checked — no full text of the source
• cites Feldmeyer et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

Neurons in a putative pre-tangle stage or with neurofibrillary tangles in intermediate stages may not be affected (or they may be only slightly affected) or they may be in a reversible state.

“These observations suggest that neurons in a putative pre-tangle stage or with neurofibrillary tangles in intermediate stages may not be affected (or they may be only slightly affected) or they may be in a reversible state.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In animal models, changes in the neck length of dendritic spines affect the temporal compartmentalization of calcium and other second messengers, changes that may affect the induction of long-term potentiation.

“In animal models, changes in the neck length of dendritic spines affects the temporal compartmentalization of calcium and other second messengers, changes that may affect the induction of long-term potentiation (Yuste, 2010; Bloodgood and Sabatini, 2005).”

• cites Yuste, 2010 sourceNot checked — no full text of the source
• cites Bloodgood and Sabatini, 2005 sourceNot checked — no full text of the source

May combine two claims.

Tau phosphorylation at the site recognized by the antibody AT8 may be a suitable marker for the initial steps of degeneration, as increased tau aggregation can subsequently be found in some neurons and it can be readily visualized with the PHF-1 tau antibody.

“This may be a suitable marker for the initial steps of degeneration, as increased tau aggregation can subsequently be found in some neurons and it can be readily visualized with the PHF-1 tau antibody (PHF-tauPHF-1).”

May combine two claims.

Cellulipetal disconnection may occur and the functional consequences of such a process are likely to be selective and progressive in the cerebral cortex as a whole, at least at the cellular level.

“These observations suggest that cellulipetal disconnection may occur and that the functional consequences of such a process are likely to be selective and progressive in the cerebral cortex as a whole, at least at the cellular level.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The selective and progressive functional consequences of cellulipetal disconnection may also occur in other cortical regions.

“This is not only evident for the proximal, intermediate and distal dendrites of pyramidal neurons in the hippocampus, where neurons in all cornu ammonis fields establish different types of synaptic contacts in each strata that they traverse (Andersen et al., 2007), but it may also occur in other cortical regions.”

• cites Andersen et al., 2007Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The morphology of a dendritic spine determines its synaptic strength and learning rules.

“Therefore, the morphology of a dendritic spine determines its synaptic strength and learning rules.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Neurons in all cornu ammonis fields establish different types of synaptic contacts in each strata that they traverse.

“This is not only evident for the proximal, intermediate and distal dendrites of pyramidal neurons in the hippocampus, where neurons in all cornu ammonis fields establish different types of synaptic contacts in each strata that they traverse (Andersen et al., 2007), but it may also occur in other cortical regions.”

• cites Andersen et al., 2007Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The sequential loss of dendritic spines in association with intracellular tau pathology appears distinct from that found in the presence of amyloid-β plaques, where dendritic regions close to extracellular plaques are depleted of dendritic spines irrespective of whether they are proximal or distal to the soma.

“This sequential loss of dendritic spines appears to be distinct to that found in the presence of amyloid-β plaques, where the dendritic regions close to the extracellular plaques are depleted of dendritic spines irrespective of whether they are proximal or distal to the soma (Knafo et al., 2009a).”

• cites Knafo et al., 2009aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Such variation could reflect different steps in the process of neuronal degeneration.

“Such variation could reflect different steps in the process of neuronal degeneration.”