Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

Lleó, Alberto; Alcolea, Daniel; Martínez-Lage, Pablo; Scheltens, Philip; Parnetti, Lucilla; Poirier, Judes; Simonsen, Anja Hviid; Verbeek, Marcel M.; Rosa‐Neto, Pedro; Slot, Rosalinde E.R.; Tainta, Mikel; Izaguirre, Andréa Gomes Coelho; Reijs, Babette L.R.; Farotti, Lucia; Tsolaki, Magda; Vandenbergue, Rik; Freund‐Levi, Yvonne; Verhey, Frans R.J.; Clarimón, Jordi; Fortea, Juan; Frölich, Lutz; Santana, Isabel; Molinuevo, José Luís; Lehmann, Sylvain; Visser, Pieter Jelle; Teunissen, Charlotte E.; Zetterberg, Henrik; Blennow, Kaj

doi:10.1016/j.jalz.2019.01.015

Cited by 102 publications

(84 citation statements)

References 47 publications

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“…Thus, the current analyses are consistent with the proposed model of progression of AD, according to which the accumulation of amyloid‐beta and tau, together with hypometabolism, lead to cognitive decline . Note, though, that there are conflicting observations regarding the correlation between Aß 1‐42 levels and deterioration in cognitive functions, and similar inconclusive evidence for longitudinal changes in p‐tau both in individuals with MCI and in individuals with AD . These observations might explain why testing time had no significant effect on CSF measures in the current analysis.…”

Section: Discussionsupporting

confidence: 86%

“…29 Note, though, that there are conflicting observations regarding the correlation between Aß 1-42 levels and deterioration in cognitive functions, 30 and similar inconclusive evidence for longitudinal changes in p-tau both in individuals with MCI and in individuals with AD. 31 These observations might explain why testing time had no significant effect on CSF measures in the current analysis.…”

Section: Discussionmentioning

confidence: 78%

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Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Bregman

Kavé

Zeltzer

et al. 2020

Int J Geriat Psychiatry

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Objectives The aim of this study was to examine whether the discrepancy between participant and informant estimation of memory decline can predict MCI prognosis. Methods Analyses involved data from individuals with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire. Participants who underestimated (N = 112) and overestimated (N = 157) their memory decline were compared on memory tasks, brain volume, and cerebrospinal markers, at study entry and after 24 months. Results Individuals who underestimated their memory decline performed more poorly on memory tests, had smaller hippocampus volume, and greater Alzheimer's disease pathology than did individuals who overestimated their cognitive decline. Longitudinal comparisons demonstrated that individuals who underestimated their decline deteriorated more significantly in memory and in brain measures. Conclusions Underestimation of memory decline should raise clinicians' suspicion of the existence of AD pathology in individuals with MCI.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 78%

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Bregman

Kavé

Zeltzer

et al. 2020

Int J Geriat Psychiatry

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“…Since bloodbrain barrier (BBB) dysfunction is related to WM damage [104] and CHI3L1 is related to BBB disruption [105], we suggest that increased CHI3L1 expression in perivascular astrocytes is an attempt to remodel the blood vasculature. Perhaps a breakdown of the BBB increases CSF CHI3L1 levels, which in turn is related to cognitive dysfunction in preclinical AD [106].…”

Section: Discussionmentioning

confidence: 99%

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease

Moreno‐Rodríguez

Perez

Nadeem

et al. 2020

J Neuroinflammation

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Background: Chitinase 3-like 1 (CHI3L1), chitinase 3-like 2 (CHI3L2), and neuronal pentraxin II (NPTX2) are inflammatory biomarkers of Alzheimer's disease (AD). Although studies have demonstrated that cerebrospinal fluid levels of these proteins are changed in AD, no studies have undertaken a detailed examination of alterations in protein levels, cellular expression, and interaction with amyloid in the brain during the progression of AD. Methods:The study evaluated levels of both CHI3L1 and CHI3L2, NPTX2, ionized calcium-binding adapter molecule 1 (Iba1), complement component 1q (C1q), glial fibrillary acidic protein (GFAP), and CD44, in the frontal cortex of people who died with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD (mAD), and severe AD (sAD) using immunoblot and immunohistochemical techniques.Results: CHI3L1-immunoreactive (-ir) astrocyte numbers were increased in the frontal cortex and white matter in sAD compared to NCI. On the other hand, increases in GFAP and Iba1-ir cell numbers were observed in MCI compared to NCI but only in white matter. Western blot analyses revealed significantly lower frontal cortex CHI3L2 levels, whereas CD44 levels were increased in sAD. No significant differences for CHI3L1, GFAP, C1q, and NPTX2 protein levels were detected between clinical groups. Strong significant correlations were found between frontal cortex CHI3L1 and Iba1-ir cell numbers in white matter and CHI3L1 and C1q protein levels in the early stages of the disease. C1q and Iba1, CD44 with CHI3L2, and GFAP protein levels were associated during disease progression. CHI3L1 and Iba1 cell numbers in white matter showed a significant associations with episodic memory and perceptual speed.Conclusions: White matter CHI3L1 inflammatory response is associated with cognitive impairment early in the onset of AD.

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“…The levels were also higher in the MCI+ group compared to the Aβ-(CN and MCI) groups. Longitudinally, CSF Ng or Brain Ng significantly decreased in the AD+ group or AD patients [13][14].…”

Section: Introductionmentioning

confidence: 90%

Clinical Utility of the Pathogenesis-related Proteins in Alzheimer’s Disease

Zhou

Fukushima²

2020

Preprint

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The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

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Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

Cited by 102 publications

References 47 publications

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease

Clinical Utility of the Pathogenesis-related Proteins in Alzheimer’s Disease

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Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

Cited by 102 publications

References 47 publications

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease

Clinical Utility of the Pathogenesis-related Proteins in Alzheimer&rsquo;s Disease

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Product

Resources

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Clinical Utility of the Pathogenesis-related Proteins in Alzheimer’s Disease