Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

Vidal-Piñeiro, Dídac; Sørensen, Øystein; Blennow, Kaj; Capogna, Elettra; Halaas, NB; Idland, AV; Mowinckel, Athanasia M.; Jb, Pereira; Lo, Wahlund; Zetterberg, Henrik; Kb, Walhovd; Fjell, Anders Martin

doi:10.1016/j.neurobiolaging.2022.04.010

Cited by 7 publications

(8 citation statements)

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“…indicated that CSF levels of FAPB3 predict brain atrophy among older cognitively healthy individuals, independent of biomarkers of amyloidopathy and tauopathy. 31 Hoglund et al. noted higher levels of CSF FABP3 in cognitively healthy individuals at risk of developing AD—those who were CSF Aβ+ (CSF Aβ below the threshold).…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid levels of fatty acid–binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Dhiman

Villemagne

Fowler

et al. 2022

Alz & Dem Diag Ass & Dis Mo

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Introduction Fatty acid–binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis—a notable Alzheimer's disease (AD) pathophysiological change. We assessed the association of cerebrospinal fluid (CSF) FABP3 levels with brain amyloidosis and the likelihood/risk of developing amyloidopathy in cognitively healthy individuals. Methods FABP3 levels were measured in CSF samples of cognitively healthy participants, > 60 years of age ( n = 142), from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL). Results FABP3 levels were positively associated with baseline brain amyloid beta (Aβ) load as measured by standardized uptake value ratio (SUVR, standardized β = 0.22, P = .009) and predicted the change in brain Aβ load (standardized β = 0.32, P = .004). Higher levels of CSF FABP3 (above median) were associated with a likelihood of amyloidopathy (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.12 to 4.65, P = .023). Discussion These results support inclusion of CSF FABP3 as a biomarker in risk‐prediction models of AD.

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Section: Discussionmentioning

confidence: 99%

“…Vidal‐Pinerio et al. indicated that CSF levels of FAPB3 predict brain atrophy among older cognitively healthy individuals, independent of biomarkers of amyloidopathy and tauopathy 31 . Hoglund et al.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid levels of fatty acid–binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Dhiman

Villemagne

Fowler

et al. 2022

Alz & Dem Diag Ass & Dis Mo

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“…FABP3 is detected at high levels in cortical neurons 35 and CSF levels are increased after trauma to the brain such as acute stroke, traumatic brain injury, and Creutzfeldt‐Jakob disease likely through release by damaged cells, making FABP3 a putative biomarker for neuronal damage 36 . However, CSF levels of FABP3 may not simply reflect generalized neuronal degeneration in AD as levels are associated with Aβ pathology and risk factors associated with AD, predict development of AD in healthy individuals, and correlate with CSF tau and apolipoprotein levels 30,37–39 . FABP3 is a fatty acid‐binding protein facilitating intracellular transport of omega‐6 polyunsaturated fatty acids (PUFAs), which participate in the regulation of the lipid composition of membranes, neurite formation, and synapse plasticity 40 .…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid biomarker profiling of diverse pathophysiological domains in Alzheimer's disease

Trombetta,

Wu,

Kuo

et al. 2024

A&D Transl Res & Clin Interv

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INTRODUCTIONWhile Alzheimer's disease (AD) is defined by amyloid‐β plaques and tau tangles in the brain, it is evident that many other pathophysiological processes such as inflammation, neurovascular dysfunction, oxidative stress, and metabolic derangements also contribute to the disease process and that varying contributions of these pathways may reflect the heterogeneity of AD. Here, we used a previously validated panel of cerebrospinal fluid (CSF) biomarkers to explore the degree to which different pathophysiological domains are dysregulated in AD and how they relate to each other.METHODSTwenty‐five CSF biomarkers were analyzed in individuals with a clinical diagnosis of AD verified by positive CSF AD biomarkers (AD, n = 54) and cognitively unimpaired controls negative for CSF AD biomarkers (CU‐N, n = 26) using commercial single‐ and multi‐plex immunoassays.RESULTSWe noted that while AD was associated with increased levels of only three biomarkers (MMP‐10, FABP3, and 8OHdG) on a group level, half of all AD participants had increased levels of biomarkers belonging to at least two pathophysiological domains reflecting the diversity in AD. LASSO modeling showed that a panel of FABP3, 24OHC, MMP‐10, MMP‐2, and 8OHdG constituted the most relevant and minimally correlated set of variables differentiating AD from CU‐N. Interestingly, factor analysis showed that two markers of metabolism and oxidative stress (24OHC and 8OHdG) contributed independent information separate from MMP‐10 and FABP3 suggestive of two independent pathophysiological pathways in AD, one reflecting neurodegeneration and vascular pathology, and the other associated with metabolism and oxidative stress.DISCUSSIONBetter understanding of the heterogeneity among individuals with AD and the different contributions of pathophysiological processes besides amyloid‐β and tau will be crucial for optimizing personalized treatment strategies.Highlights A panel of 25 highly validated biomarker assays were measured in CSF. MMP10, FABP3, and 8OHdG were increased in AD in univariate analysis. Many individuals with AD had increased levels of more than one biomarker. Markers of metabolism and oxidative stress contributed to an AD multianalyte profile. Assessing multiple biomarker domains is important to understand disease heterogeneity.

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“…Third, HFABP may also regulate dopamine D2R (dopamine receptor 2) function in the striatum and anterior cingulate cortex and mediates αSyn neurotoxicity in septal GABAergic neurons to affect cognitive function and emotional behavior (Yamamoto et al, 2018;Matsuo et al, 2021). Finally, recent studies suggested HFABP was associated with specific features of brain atrophy and white matter Hyperintensities burden, independently of amyloid and tau pathology biomarkers (Clark et al, 2022;Vidal-Piñeiro et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes

Wang

Huang

et al. 2022

Front. Aging Neurosci.

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BackgroundPerturbation of lipid metabolism is associated with Alzheimer’s disease (AD). Heart fatty acid-binding protein (HFABP) is an adipokine playing an important role in lipid metabolism regulation.Materials and methodsTwo datasets separately enrolled 303 and 197 participants. First, we examine the associations of cerebrospinal fluid (CSF) HFABP levels with cognitive measures [including Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of boxes (CDRSB), and the cognitive section of Alzheimer’s Disease Assessment Scale] and AD biomarkers (CSF amyloid beta and tau levels). Second, we examine the longitudinal associations of baseline CSF HFABP levels and the variability of HFABP with cognitive measures and AD biomarkers. Structural equation models explored the mediation effects of AD pathologies on cognition.ResultsWe found a significant relationship between CSF HFABP level and P-tau (dataset 1: β = 2.04, p < 0.001; dataset 2: β = 1.51, p < 0.001). We found significant associations of CSF HFABP with longitudinal cognitive measures (dataset 1: ADAS13, β = 0.09, p = 0.008; CDRSB, β = 0.10, p = 0.003; MMSE, β = −0.15, p < 0.001; dataset 2: ADAS13, β = 0.07, p = 0.004; CDRSB, β = 0.07, p = 0.005; MMSE, β = −0.09, p < 0.001) in longitudinal analysis. The variability of HFABP was associated with CSF P-tau (dataset 2: β = 3.62, p = 0.003). Structural equation modeling indicated that tau pathology mediated the relationship between HFABP and cognition.ConclusionOur findings demonstrated that HFABP was significantly associated with longitudinal cognitive changes, which might be partially mediated by tau pathology.

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Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

Cited by 7 publications

References 70 publications

Cerebrospinal fluid levels of fatty acid–binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Cerebrospinal fluid levels of fatty acid–binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Cerebrospinal fluid biomarker profiling of diverse pathophysiological domains in Alzheimer's disease

Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes

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