A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases.

14 September, 2023

ABSTRACT Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ immunotherapies for Alzheimer’s disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or

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Cognitive effects of Lewy body pathology in clinically unimpaired individuals.

ABSTRACT α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer’s disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182

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Clinical effects of Lewy body pathology in cognitively impaired individuals.

ABSTRACT There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer’s disease (AD) pathology (amyloid-β and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from

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CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease.

ABSTRACT Aggregated insoluble tau is one of two defining features of Alzheimer’s disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that

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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring.

ABSTRACT Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used

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Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline.

ABSTRACT A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer’s disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325),

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Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology.

11 September, 2023

Nat Aging. 2022 Dec;2(12):1138-1144. doi: 10.1038/s43587-022-00310-z.

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Associations of CSF PDGFRβ With Aging, Blood-Brain Barrier Damage, Neuroinflammation, and Alzheimer Disease Pathologic Changes.

Neurology. 2023 Jul 4;101(1):e30-e39. doi: 10.1212/WNL.0000000000207358.

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Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.

Alzheimer’s Disease Neuroimaging Initiative. JAMA Neurol. 2023 Jun 1;80(6):614-623. doi: 10.1001/jamaneurol.2023.1067.

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Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer’s disease.

Alzheimers Dement. 2023 Apr 27. doi: 10.1002/alz.13103

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Clinical Utility of Tau Positron Emission Tomography in the Diagnostic Workup of Patients With Cognitive Symptoms.

JAMA Neurol. 2023 Jul 1;80(7):749-756. doi: 10.1001/jamaneurol.2023.1323.

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Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders.

Aust N Z J Psychiatry. 2023 Jul 21:48674231187312. doi: 10.1177/00048674231187312.

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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.

Nat Immunol. 2023 Sep;24(9):1540-1551. doi: 10.1038/s41590-023-01588-w.

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