Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy

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

YKL-40 is mainly expressed by astrocytes, but also by microglia, often in close vicinity to senile plaques and neurofibrillary tangles.

“YKL-40 is mainly expressed by astrocytes, but also by microglia, often in close vicinity to senile plaques and neurofibrillary tangles [15–17].”

• cites [15] Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ, et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry. 2010;68(10):903–12. https://doi.org/10.1016/j.biopsych.2010.08.025. sourceDisputed

  The Results section reports YKL-40 in astrocytes near amyloid plaques, but explicitly says it was not observed in the microglia identified by either marker. It reports occasional neurofibrillary tangles in rare YKL-40-positive white-matter neurons, not as evidence of expression by microglia near tangles. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [16] Querol-Vilaseca M, Colom-Cadena M, Pegueroles J, San Martín-Paniello C, Clarimon J, Belbin O, et al. YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer’s disease and other tauopathies. J Neuroinflammation. 2017;14(1):118. https://doi.org/10.1186/s12974-017-0893-7. sourcePartly supported

  The Results report that 75–85% of YKL-40 immunoreactivity colocalized with an astroglial marker, supporting the astrocyte portion of the claim. But the Results found no colocalization with a microglial marker, and the Discussion says the authors did not detect YKL-40 in microglia. The paper does not establish that YKL-40-positive cells are often close to senile plaques or neurofibrillary tangles; it describes the astrocytes as mainly isolated. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [17] Bonneh-Barkay D, Bissel SJ, Kofler J, Starkey A, Wang G, Wiley CA. Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathol. 2012;22(4):530–46. https://doi.org/10.1111/j.1750-3639.2011.00550.x. sourcePartly supported

  The Results section reports YKL-40 expression in reactive astrocytes in the examined neuroinflammatory conditions, supporting the astrocyte portion of the claim. It reports no YKL-40 staining in the examined parenchymal microglia, and does not address proximity to senile plaques or neurofibrillary tangles. No page numbers are available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

NLK may support survival of sensory and spinal neurons and stimulate axonal growth.

“may support survival of sensory and spinal neurons and stimulate axonal growth [10–13]”

• cites [10] Gurney ME, Apatoff BR, Heinrich SP. Suppression of terminal axonal sprouting at the neuromuscular junction by monoclonal antibodies against a muscle-derived antigen of 56,000 daltons. J Cell Biol. 1986;102(6):2264–72. https://doi.org/10.1083/jcb.102.6.2264. sourcePartly supported

  The discussion (page not identified in our copy) associates the 56-kD antigen with spinal-neuron survival activity in culture, and reports that antibodies against it suppress motor-axon terminal sprouting. It does not identify the antigen as NLK or report that it supports sensory-neuron survival, so those parts of the claim are not established by this paper. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [11] Deng L, Shi B, Zhuang Y, Chu J, Shi X, Zhang S, et al. Performance and mechanism of neuroleukin in the growth and survival of sertoli cell-induced neurons in a coculture system. Cell Transplanti J. 2014;23(3):381–94. https://doi.org/10.3727/096368913X663578. sourceNot checked — no full text of the source
• cites [12] Gurney MEM. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986;234(4776):566–74. https://doi.org/10.1126/science.3764429. sourceNot checked — no full text of the source
• cites [13] Tanie Y, Tanabe N, Kuboyama T, Tohda C. Extracellular neuroleukin enhances neuroleukin secretion from astrocytes and promotes axonal growth in vitro and in vivo. Front Pharmacol. 2018;9:1228. https://doi.org/10.3389/fphar.2018.01228. sourcePartly supported

  The Introduction (page unavailable) reports pro-survival effects of NLK in cultured sensory neurons, and the Results report increased axonal density in cultured cortical neurons and spinal-cord-injured mice. The paper does not report a survival effect specifically in spinal neurons, so that part of the claim is not established by our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

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

Genome-wide association studies have identified associations between inflammation- and immune-related variants in genes (such as a missense mutation in TREM2) and increased AD risk.

“In addition, genome-wide association studies have identified associations between inflammation- and immune-related variants in genes (such as a missense mutation in the gene encoding for TREM2, a receptor expressed on microglia) and increased AD risk [36].”

• cites [36] Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77(1):43–51. https://doi.org/10.1016/j.biopsych.2014.05.006. sourcePartly supported

  The Immune Response section reports GWAS associations for several immune-related genes, and its TREM2 subsection reports that rare missense TREM2 variants increase late-onset AD risk. But the Immune Response section says TREM2 coding variants were identified in sequencing studies, not GWAS; the Emerging Genetics section explicitly distinguishes those methods. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

In the extracellular space, NLK supports neuronal survival and stimulates axonal growth.

“In the extracellular space NLK supports neuronal survival and stimulates axonal growth [10–13]”

• cites [10] Gurney ME, Apatoff BR, Heinrich SP. Suppression of terminal axonal sprouting at the neuromuscular junction by monoclonal antibodies against a muscle-derived antigen of 56,000 daltons. J Cell Biol. 1986;102(6):2264–72. https://doi.org/10.1083/jcb.102.6.2264. sourcePartly supported

  The Discussion (p. 2271) associates the soluble, muscle-derived 56-kD antigen with spinal-neuron survival activity in preliminary culture results and finds it necessary for motor-axon terminal sprouting. It does not identify the antigen as NLK or establish that it independently stimulates axonal growth; the authors explicitly leave open whether it is a sprouting factor or a necessary co-factor. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [11] Deng L, Shi B, Zhuang Y, Chu J, Shi X, Zhang S, et al. Performance and mechanism of neuroleukin in the growth and survival of sertoli cell-induced neurons in a coculture system. Cell Transplanti J. 2014;23(3):381–94. https://doi.org/10.3727/096368913X663578. sourceNot checked — no full text of the source
• cites [12] Gurney MEM. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986;234(4776):566–74. https://doi.org/10.1126/science.3764429. sourceNot checked — no full text of the source
• cites [13] Tanie Y, Tanabe N, Kuboyama T, Tohda C. Extracellular neuroleukin enhances neuroleukin secretion from astrocytes and promotes axonal growth in vitro and in vivo. Front Pharmacol. 2018;9:1228. https://doi.org/10.3389/fphar.2018.01228. sourceSupported

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

Aβ may initiate microglial activation, resulting in microglial migration to plaques, phagocytosis, and enzymatic degradation of Aβ.

“Furthermore, Aβ may initiate microglial activation, resulting in microglial migration to plaques, phagocytosis, and enzymatic degradation of Aβ [37].”

• cites [37] Heneka MT, Carson MJ, Khoury JE, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405. https://doi.org/10.1016/S1474-4422(15)70016-5. sourceSupported

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

Previous immunohistochemical studies in AD patients and in a transgenic rat model of CAA have found that CAA type 1, i.e., amyloid deposition in the capillary vessels, was associated with perivascular inflammation.

“On the other hand, previous immunohistochemical studies in AD patients and in a transgenic rat model of CAA have found that CAA type 1, i.e., amyloid deposition in the capillary vessels, was associated with perivascular inflammation [39, 40].”

• cites [39] Zhu X, Hatfield J, Sullivan JK, Xu F, Van Nostrand WE. Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy. J Neuroinflammation. 2020;17(1):78. https://doi.org/10.1186/s12974-020-01755-y. sourceSupported
• cites [40] Richard E, Carrano A, Hoozemans JJ, van Horssen J, van Haastert ES, Eurelings LS, et al. Characteristics of dyshoric capillary cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2010;69(11):1158–67. https://doi.org/10.1097/NEN.0b013e3181fab558. sourceNot checked — no full text of the source

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

Prolonged microglial activation may be detrimental, leading to a self-perpetuating cycle involving production of neurotoxic pro-inflammatory cytokines, damaging neurons, inducing more recruitment of microglia, further increasing their activation and release of pro-inflammatory cytokines.

“Prolonged microglial activation may be detrimental, since it eventually leads to a self-perpetuating cycle involving the production of neurotoxic pro-inflammatory cytokines, damaging neurons, inducing more recruitment of microglia, further increasing their activation and release of pro-inflammatory cytokines [35].”

• cites [35] Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018;4(1):575–90. https://doi.org/10.1016/j.trci.2018.06.014. sourceSupported

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

Inflammation does not seem to be a major component in CAA-related microhemorrhage or microinfarction, with the exception of a rare clinical subtype: CAA-related inflammation.

“Inflammation does, however, not seem to be a major component in CAA-related microhemorrhage or microinfarction [38], with the exception of a rare clinical subtype: CAA-related inflammation [6].”

• cites [38] van Veluw SJ, Scherlek AA, Freeze WM, Ter Telgte A, van der Kouwe AJ, Bacskai BJ, et al. Different microvascular alterations underlie microbleeds and microinfarcts. Ann Neurol. 2019;86(2):279–92. https://doi.org/10.1002/ana.25512. sourcePartly supported

  The Discussion (page unavailable) argues against local inflammatory responses as an explanation for the vessel-wall changes observed around microbleeds. It does not assess whether inflammation is a major component of CAA-related microinfarction, or rule it out generally for microhemorrhage. The rare inflammatory subtype is attached to a different citation in the citing sentence. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [6] Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways. Nat Rev Neurol. 2020;16(1):30–42. https://doi.org/10.1038/s41582-019-0281-2. sourceSupported

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

Chronic microglial inflammation has been observed in the brains of AD patients at various disease stages, and pro-inflammatory cytokines such as IL-1β, IL-2, IL-6, and tumor necrosis factor-α have been shown to be upregulated in AD.

“Chronic microglial inflammation has been observed in the brains of AD patients at various disease stages, and pro-inflammatory cytokines such as IL-1β, IL-2, IL-6, and tumor necrosis factor-α have been shown to be upregulated in AD [35].”

• cites [35] Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018;4(1):575–90. https://doi.org/10.1016/j.trci.2018.06.014. sourcePartly supported

  The Overview describes chronic neuroinflammation in AD as involving activated microglia. The Specific cytokine signaling in AD section reports elevated IL-1β, IL-6, and TNF-α in AD patients, including IL-1β in both MCI and AD. Our copy does not establish that IL-2 is upregulated in AD, so the full cytokine list is not supported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

CSF NLK correlated with age.

“Again, NLK correlated with age (rSP = 0.43, p < 0.0001) and with total protein (rSP = 0.32, p < 0.0001).”

May combine two claims.

CSF NLK levels were increased in aMCI patients and in AD patients, as established in two independent samples from two different centers.

“The main findings of our study are as follows: (1) CSF NLK levels were increased in aMCI patients and in AD patients, as established in two independent samples from two different centers.”

• Also stated in: § Conclusions · plain

  “We conclude that CSF NLK is increased in aMCI and AD patients, but not in CAA patients, which indicates that it is a marker associated with early stage AD.”

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

Controls were significantly younger than the aMCI patients and AD patients.

“Furthermore, controls were significantly younger than the aMCI patients and AD patients.”

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

Additional adjustment for CSF total protein yielded similar results in Barcelona.

“Additional adjustment for CSF total protein yielded similar results (p = 0.013 and p = 0.005, respectively).”

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

The increase in NLK mRNA in cultured human brain pericytes after exposure to Aβ40 may represent an attempt to survive Aβ-induced cell death.

“which may represent an attempt to survive Aβ-induced cell death”

• cites [8] Rensink AAM, Otte-Höller I, Donkelaar HJ, De Waal RMW, Kremer B, Verbeek MM. Differential gene expression in human brain pericytes induced by amyloid-β protein. Neuropathol Appl Neurobiol. 2004;30(3):279–91. https://doi.org/10.1111/j.1365-2990.2004.00536.x. sourceNot checked — no full text of the source

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

The technician performing CSF analyses was blinded for clinical diagnoses, and patient and control samples were randomly analyzed.

“For all CSF analyses, the technician who performed the analysis was blinded for the clinical diagnoses, and patient and controls samples were randomly analyzed to overcome bias.”

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

In the Barcelona cohort, sex distribution was similar but aMCI and AD patients were older than controls.

“Sex distribution was similar, whereas aMCI (mean age 70 ± 3 year, 30% male), and AD patients (mean age 67 ± 7 years, 47% male) were older (p < 0.0001 and p = 0.002) than the control subjects (mean age 63 ± 4 years, 50% male; Table 3).”

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

Each MRI was rated independently by two trained raters, with good agreement (weighted Cohen's κ 0.69 for GCA and 0.73 for MTA).

“Each MRI was rated independently by two trained raters (AK and LR), and there was a good agreement between the two raters: a weighted Cohen’s κ of 0.69 for GCA and 0.73 for MTA.”

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

The mean intra-assay CV was 3.6 ± 3.6% and inter-assay CV was 4.9 ± 2.9%.

“The mean intra-assay coefficient of variation (CV) for CSF samples (duplicate measures) was 3.6 ± 3.6% and the mean inter-assay CV was 4.9 ± 2.9%.”

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

MRI images were reviewed blinded to all clinical and CSF data.

“MRI images were reviewed blinded to all clinical and CSF data and scored for medial temporal lobe atrophy (MTA) [29] and global cortical atrophy (GCA) [30].”

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

Additional adjustment for CSF total protein did not affect the results in CAA.

“Additional adjustment for CSF total protein did not affect the results (p = 0.34).”

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

The NLK ELISA had a lower limit of detection of 61 pg/ml and all CSF measures were above it.

“The lower limit of detection (LLOD) of the NLK ELISA was 61 pg/ml. All CSF measures were above the LLOD.”

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

NLK is present in senile plaques and Aβ-laden vessels in AD.

“NLK expression was found in senile plaques and in Aβ-laden vessels [8]”

• cites [8] Rensink AAM, Otte-Höller I, Donkelaar HJ, De Waal RMW, Kremer B, Verbeek MM. Differential gene expression in human brain pericytes induced by amyloid-β protein. Neuropathol Appl Neurobiol. 2004;30(3):279–91. https://doi.org/10.1111/j.1365-2990.2004.00536.x. sourceNot checked — no full text of the source

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

Ethical approval was obtained from the relevant committees.

“This study was approved by the Medical Ethics Committee Arnhem-Nijmegen (file nos. 2016-3011 and 2014-1401), Ethical Committee of IIB-Sant Pau (16/2013), and Partners Human Research Committee of Boston (study ID PHRC #2006P000664).”

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

Messenger RNA levels of NLK are increased in cultured human brain pericytes after exposure to Aβ40.

“messenger RNA levels of NLK were increased in cultured human brain pericytes after exposure to Aβ40 [8]”

• cites [8] Rensink AAM, Otte-Höller I, Donkelaar HJ, De Waal RMW, Kremer B, Verbeek MM. Differential gene expression in human brain pericytes induced by amyloid-β protein. Neuropathol Appl Neurobiol. 2004;30(3):279–91. https://doi.org/10.1111/j.1365-2990.2004.00536.x. sourceNot checked — no full text of the source

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

Five quality controls were included on each plate in each test run to correct for inconsistencies between plates.

“In all NLK and total protein CSF analyses, five quality controls were included on each plate in each test run to correct for any inconsistencies between plates.”

Classified as probably not a substantial claim.

Group differences in NLK levels were adjusted for age and sex.

“When comparing group differences of NLK levels, we adjusted for age and sex by performing multiple regression analysis with patient group, age and sex as independent variables.”

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

In the Nijmegen cohort, sex distribution was similar but aMCI and AD patients were older than controls.

“Sex distribution was similar, whereas aMCI (median age 72 [70–78] years, 37% male) and AD patients (median age 74 [65–77] years, 28% male) were older (both p < 0.0001) than the control subjects (median age 61 [56–67] years, 47% male; Table 2).”

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

Plate variation was corrected using quality control measurements.

“The variation between the ELISA plates, based on quality control measurements, ranged from a factor 0.89 to 1.08, for which the CSF measures were corrected accordingly, by recalculating the results using the results of one plate as a reference.”

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

Group differences in NLK levels were additionally adjusted for CSF total protein.

“In a second model, we adjusted for age, sex, and CSF total protein levels.”

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

NLK can serve as a neurotrophic growth factor.

“it was shown that NLK can serve as a neurotrophic growth factor [9]”

• cites [9] Gurney M, Apatoff B, Spear G, Baumel M, Antel J, Bania M, et al. Neuroleukin: a lymphokine product of lectin-stimulated T cells. Science. 1986;234(4776):574–81. https://doi.org/10.1126/science.3020690. sourceNot checked — no full text of the source

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

CSF YKL-40 is an established neuroinflammatory marker.

“CSF YKL-40 (also known as chitinase-3 like-protein 1 or cartilage glycoprotein-39) is an established neuroinflammatory marker [14].”

• cites [14] Baldacci F, Lista S, Cavedo E, Bonuccelli U, Hampel H. Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases. Expert Rev Proteomics. 2017;14(4):285–99. https://doi.org/10.1080/14789450.2017.1304217. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

We only have the availability of MMSE scores in a subset of CAA patients.

“However, since we only have the availability of MMSE scores in a subset of CAA patients, we should interpret these data with caution.”

Classified as probably not a substantial claim.

NLK is possibly involved in a neuroprotective response to neuronal damage caused by AD pathology.

“NLK is a neurotrophic factor, possibly involved in a neuroprotective response to neuronal damage caused by AD pathology.”

• AssumptionRests on an assumption: CSF NLK levels reflect cerebral NLK production/activity.

Classified as probably not a substantial claim.

The Barcelona cohort serves as a validation cohort.

“The Barcelona cohort serves as a validation cohort”

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

Lack of detailed information on the cognitive status of CAA patients obstructed systematic analysis of this as a possible confounding factor for the analysis of NLK levels.

“In addition, the lack of detailed information on the cognitive status of CAA patients obstructed us from systematically analyzing this as a possible confounding factor for the analysis of NLK levels.”

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

In an immunohistochemical study in AD patients, NLK expression was found in neurons, microglia, and oligodendroglia, and in the vessel wall, specifically in cerebrovascular cells such as smooth muscle cells.

“In an immunohistochemical study in AD patients, NLK expression was found in neurons, microglia, and oligodendroglia, and in the vessel wall, specifically in cerebrovascular cells such as smooth muscle cells [8].”

• cites [8] Rensink AAM, Otte-Höller I, Donkelaar HJ, De Waal RMW, Kremer B, Verbeek MM. Differential gene expression in human brain pericytes induced by amyloid-β protein. Neuropathol Appl Neurobiol. 2004;30(3):279–91. https://doi.org/10.1111/j.1365-2990.2004.00536.x. sourceNot checked — no full text of the source

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

YKL-40 is an established neuroinflammatory marker, expressed by astrocytes and microglia.

“CSF NLK strongly correlated with CSF YKL-40 (also known as chitinase-3 like-protein 1 or cartilage glycoprotein-39), an established neuroinflammatory marker [14], expressed by astrocytes and microglia.”

• cites [14] Baldacci F, Lista S, Cavedo E, Bonuccelli U, Hampel H. Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases. Expert Rev Proteomics. 2017;14(4):285–99. https://doi.org/10.1080/14789450.2017.1304217. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

NLK is a neurotrophic factor.

“NLK is a 56-kDa multifunctional protein named after two of its functions: it can act as a neurotrophic factor and as a lymphokine [12].”

• Also stated in: § Conclusions · plain

  “NLK is a neurotrophic factor, possibly involved in a neuroprotective response to neuronal damage caused by AD pathology.”

• cites [12] Gurney MEM. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986;234(4776):566–74. https://doi.org/10.1126/science.3764429. sourceNot checked — no full text of the source

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

NLK can act as a lymphokine.

“NLK is a 56-kDa multifunctional protein named after two of its functions: it can act as a neurotrophic factor and as a lymphokine [12].”

• cites [12] Gurney MEM. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986;234(4776):566–74. https://doi.org/10.1126/science.3764429. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

We previously demonstrated by immunohistochemistry that NLK may be associated with CAA pathology.

“We previously demonstrated by immunohistochemistry that NLK may be associated with CAA pathology [8], but apparently this association is not reflected by an increase of NLK in the CSF.”

• cites [8] Rensink AAM, Otte-Höller I, Donkelaar HJ, De Waal RMW, Kremer B, Verbeek MM. Differential gene expression in human brain pericytes induced by amyloid-β protein. Neuropathol Appl Neurobiol. 2004;30(3):279–91. https://doi.org/10.1111/j.1365-2990.2004.00536.x. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

We were able to validate our findings in two independent aMCI/AD samples.

“Another important strength is that we were able to validate our findings in two independent aMCI/AD samples.”

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

Our group sizes were relatively small.

“Our group sizes were relative small, but a strength of our study is the inclusion of aMCI/AD and controls subjects with thorough clinical evaluation, for many of whom imaging and AD biomarker data was also available.”

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

We did not have YKL-40 levels available for the Nijmegen CAA, AD patients, and controls.

“A limitation of this study is that we did not have YKL-40 levels available for the Nijmegen CAA, AD patients, and controls.”

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

The study included aMCI/AD and control subjects with thorough clinical evaluation, for many of whom imaging and AD biomarker data was also available.

“Our group sizes were relative small, but a strength of our study is the inclusion of aMCI/AD and controls subjects with thorough clinical evaluation, for many of whom imaging and AD biomarker data was also available.”