Blood biomarkers for cognitive decline and clinical progression in a Mexican American cohort

Gonzales, Mitzi M.; Wang, Chen‐Pin; Short, Meghan I.; Parent, Danielle; Kautz, Tiffany F.; MacCarthy, Daniel; González, David Andrés; Royall, Donald R.; Zare, Habil; O’Bryant, Sid; Maestre, Gladys E.; Tracy, Russell P.; Seshadri, Sudha

doi:10.1002/dad2.12298

Cited by 10 publications

(17 citation statements)

References 56 publications

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“…In line with our observations, plasma GFAP levels have been reported to be positively associated with cognitive dysfunction and cerebral atrophy 18,33,34 . These clinical observations t well with pathology studies that show a gradual increase of GFAP levels in the brain in relation to AD severity 35,36 .…”

Section: Discussionsupporting

confidence: 92%

“…These clinical observations t well with pathology studies that show a gradual increase of GFAP levels in the brain in relation to AD severity 35,36 . Plasma GFAP levels have also been reported to associate with longitudinal cognitive decline and cerebral atrophy, which is con rmed in our study, [37][38][39][40] and higher incident dementia risk 26,33 . Thus, familial, clinical, and population-based studies suggest that increased plasma or serum GFAP levels not only associate with, but also predict, disease progression in AD.…”

Section: Discussionsupporting

confidence: 85%

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Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Chatterjee

Vermunt

Gordon

et al. 2022

Preprint

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Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Plasma GFAP elevations appear a decade before expected symptom onset, after β-amyloid accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished β-amyloid-positive from β-amyloid-negative ADAD participants and showed a stronger relationship with β-amyloid load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Our findings support a role for plasma GFAP as a clinical biomarker for β-amyloid-associated cognitive deterioration in AD.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 85%

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Chatterjee

Vermunt

Gordon

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In line with our observations, plasma GFAP levels have been reported to be positively associated with cognitive dysfunction and cerebral atrophy 18,42,43 . These clinical observations fit well with pathology studies that show a gradual increase of GFAP levels in the brain in relation to AD severity 44,45 .…”

Section: Discussionsupporting

confidence: 92%

“…These clinical observations fit well with pathology studies that show a gradual increase of GFAP levels in the brain in relation to AD severity 44,45 . Plasma GFAP levels have also been reported to associate with longitudinal cognitive decline and cerebral atrophy, which is confirmed in our study, [46][47][48][49] and higher incident dementia risk 35,42 . Thus, familial, clinical, and population-based studies suggest that increased plasma or serum GFAP levels not only associate with, but also predict, disease progression in AD.…”

Section: Discussionsupporting

confidence: 89%

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Chatterjee

Vermunt

Gordon

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Lastly, plasma glial fibrillary acidic protein (GFAP), a marker of astrogliosis, 65 , 66 is elevated across the Alzheimer’s spectrum, 67-71 as well as other neurodegenerative diseases such as frontotemporal dementia 70 , 72 and studies report a significant correlation with cognitive functioning. 37 , 62 , 68 , 70 , 72-74 Plasma GFAP has also been reported to increase over time in cognitively unimpaired individuals; 75 , 76 however, fewer studies have investigated its relationship with cognitive functions in late-adulthood individuals without dementia. One study reported a significant inverse association with cross-sectional working memory and executive functioning, 75 and in the same cohort, a significant correlation was reported with cognitive functions at a 12-month follow-up.…”

Section: Introductionmentioning

confidence: 99%

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

Saunders

Pozzolo

Heslegrave

et al. 2023

Brain Communications

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Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181 (p-tau181), amyloid-β, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as promising biomarkers for Alzheimer’s disease. While these blood biomarkers are promising for distinguishing people with Alzheimer’s disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while p-tau181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of p-tau181, amyloid-β, NfL, and GFAP predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian Birth Cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of p-tau181 in the brain. Several forms of p-tau have been shown to contribute to synapse degeneration in Alzheimer’s disease, which correlates closely with cognitive decline in this form of dementia, but to date there have not been investigations of whether p-tau181 is found in synapses in Alzheimer’s disease or healthy ageing brain. It was also previously unclear whether p-tau181 accumulated in dystrophic neurites around plaques which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine p-tau181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localisation of p-tau181 were examined using array tomography (n = 6-15 per group), and localisation of p-tau181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma p-tau181, NfL, and GFAP predicted steeper general cognitive decline during ageing. Further, increasing p-tau181 over time predicted general cognitive decline in females only. Change in plasma p-tau181 remained a significant predictor of g factor decline when taking into account Alzheimer’s disease polygenic risk score, indicating the increase of blood p-tau181 in this cohort was not only due to incipient Alzheimer’s disease. P-tau181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer’s disease brain. We observed that a significantly higher proportion of synapses contain p-tau181 in Alzheimer’s disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more p-tau181 in GFAP-positive astrocytes than those with pre-morbid lifetime cognitive decline. Further, p-tau181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of p-tau181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma p-tau181, NfL, and GFAP may be useful biomarkers of age-related cognitive decline, and that efficient clearance of p-tau181 by astrocytes may promote cognitive resilience.

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Blood biomarkers for cognitive decline and clinical progression in a Mexican American cohort

Cited by 10 publications

References 56 publications

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

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