Biomarkers.

Background: The MarkVCID consortium was established to address the paucity of biomarkers for vascular contributions to cognitive impairment and dementia (VCID), a leading cause of dementia. Plasma neurofilament light (NfL), a neuroaxonal injury marker elevated in several neurological and neurodegenerative diseases, was selected as one of the first biomarkers to be examined. We performed comprehensive instrumental and clinical validation of the Quanterix Simoa NfL assay using the first MarkVCID cohort.

Biomarkers.

Background: We currently lack in the dementia field accurate, noninvasive, quick, and affordable screening tools for brain dysfunctions associated with early subtle risk of mild cognitive impairment (MCI). Our Kentucky aging cohort demonstrates that asymptomatic older individuals with MCI-like frontal memory-related brainwave patterns convert to MCI within a short 5-year period, as opposed to individuals with NC-like patterns (1) that remain normal 10 years later (2). Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease (3).

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: Recent research emphasizes the significance of white matter tracts and the free-water (FW) component in understanding cognitive decline. The goal of this study is to conduct a large-scale assessment on the role of white matter microstructure on longitudinal cognitive decline.

Method: This study used a cohort collated from seven longitudinal cohorts of aging (ADNI, BIOCARD, BLSA, NACC, ROS/MAP/MARS, VMAP, and WRAP).

Biomarkers.

Background: Non-invasive biofluid and MRI measures of blood-brain-barrier (BBB) dysfunction may aid early detection of cerebral small vessel disease (cSVD). Plasma markers of astrocytic function and injury, such as S100 calcium-binding protein B (S100b), have gained increased attention in relation to BBB integrity and cognition. Here we explored the inter-relationships between plasma S100b levels, an MRI measure of water exchange rate across the BBB (kw), and cognitive performance among older adults.

Biomarkers.

Background: Diet has been associated with memory, emotion/stress regulation, structure and function of the hippocampus and amygdala and attenuation of cognitive aging. There is a well-recognized lack of reliability in self-reported dietary intake and great interest in objective metabolic readout of dietary patterns. In this study we constructed dietary profiles from untargeted metabolomics data using a novel metadata-based source annotation method developed at the Dorrestein Lab, also referred to as "foodomics".

Biomarkers.

Background: Alzheimer's disease (AD) pathology occurs in the brain before manifestation of significant cognitive decline. Growing evidence suggests that brain networks such as default mode network (DMN) or salience network, identified through resting-state functional magnetic resonance imaging (MRI), are affected by AD pathology. In this study, we investigated the relationship between network segregation and the key in vivo AD pathologies including beta-amyloid (Aβ) and tau deposition in old adults with no cognitive impairment.

Biomarkers.

Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.

Biomarkers.

Background: Biorepositories play an integral role in the advancement of our understanding of neurodegenerative diseases and improving human health outcomes. Research efforts are accelerated when access to high-quality clinical specimens is made available from a large, diverse participant group. Indiana University is home to three important neurodegenerative disease-focused biorepositories including the NIA-funded National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), the NINDS-funded Biospecimen Exchange for Neurological Disorders (BioSEND), and the Michael J.

Biomarkers.

Background: The earliest recognized biomarker of AD is deposition of Aβ amyloid that leads to formation of plaques and may, over time, trigger or at least be followed by gliosis/neuroinflammation and neurofibrillary tangles, accompanied by neurodegenerative changes including neuronal and synaptic loss. We have previously reported that semaphorin 4D (SEMA4D), the major ligand of plexin B receptors expressed on astrocytes, is upregulated in diseased neurons during progression of AD and Huntington's disease (HD). Binding of SEMA4D to PLXNB receptors triggers astrocyte reactivity, leading to loss of neuroprotective homeostatic functions, including downregulation of glutamate and glucose transporters (doi:10.

Biomarkers.

Background: Tau-PET with [18F]Flortaucipir is FDA-approved for the identification of AD tau neuropathology in the differential diagnosis of patients with cognitive impairment. However, its performance in detecting early AD stages requires further assessment. We aimed to i) examine the relationships between Flortaucipir-PET and AD neuropathology, and ii) characterize the relationship between Flortaucipir-PET and emerging plasma ptau217 biomarker in autopsy cases.

Biomarkers.

Background: Brain network studies in Alzheimer's disease (AD) have primarily focused on structural and functional connectomes as separate entities. However, it remains unclear how brain structure interacts with brain function in AD.

Method: We included 75 cognitively unimpaired participants and 49 patients with AD.

Biomarkers.

Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies.

Methods: Ninety-nine cognitively unimpaired individuals from the ALFA+ cohort with valid F-RO-948 and F-flutemetamol PET, T1-weighted MRI, cognition, CSF, and plasma biomarkers were included.

Biomarkers.

Background: Vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease (AD) are the two most common forms of dementia, with overlapping risk factors including cardiovascular risk factors such as hypertension and dyslipidemia. The etiology of both VCID and AD shows sex-based differences, as well as sex-based differences in cardiovascular risk factors. However, how sex differences influence AD and angiogenic biomarkers in older adults who have high cardiovascular risk factors is not known.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: Two main risk factors of Alzheimer's disease (AD) are aging and APOE-ε4. However, some individuals remain cognitively normal despite having these risk factors. They are considered "cognitively resilient".

Biomarkers.

Primary Care (PC) clinicians are faced with numerous competing demands and priorities for maximizing patient care. These challenges make the implementation of strategies for early detection of Alzheimer's Disease (AD) complex. Few real-world implementation projects about early detection of AD in PC exist.

Biomarkers.

Background: There is growing recognition that white matter microstructural integrity is affected in Alzheimer's disease. The goal of this study was to characterize sex, racial/ethnic, and apolipoprotein (APOE)-ε4 allele differences in white matter integrity.

Methods: This study included participants from ADNI, BLSA, ROS/MAP/MARS, and VMAP, all longitudinal cohorts of aging.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: Diffusion MRI (dMRI) metrics of brain microstructure offer valuable insight into Alzheimer's disease (AD) pathology; recent reports have identified dMRI metrics that (1) tightly link with CSF or PET measures of amyloid and tau burden; and (2) mediate the relationship between CSF markers of AD and delayed logical memory performance, commonly impaired in early AD [1,2]. To better localize white matter tract disruption in AD, our BUndle ANalytic (BUAN) [3] tractometry pipeline allows principled use of statistical methods to map factors affecting microstructural metrics along the 3D length of the brain's fiber tracts. Here, we extended BUAN to pool data from multiple scanning protocols/sites - using a new harmonized tractometry approach, based on ComBat [4,5], a widely-used harmonization method modeling variations in multi-site datasets due to site- and scanner-specific effects.

Biomarkers.

Background: Apathy in patients with Alzheimer's disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD.

Method: For 1162 participants in the Alzheimer's Disease Neuroimaging Initiative, including those with AD, MCI and cognitively normal individuals, a partial least squares correspondence analysis (PLS-CA) modeled interactions between single nucleotide polymorphisms (SNPs), structural whole-brain imaging variables, and apathy.

Biomarkers.

Background: By age 40 years, adults with Down syndrome (DS) develop Alzheimer's disease (AD) pathology and progress to dementia in their 60s. Despite minimal systemic vascular risk factors, individuals with DS have MRI evidence of cerebrovascular injury that progresses with AD severity, suggesting an intrinsic vascular component to DS-AD that may interact with neuroinflammatory processes to promote tau pathology and cognitive decline. In the current study we examined whether cerebrovascular disease (CVD) burden and inflammation/astrocytosis independently and interactively were associated with incident diagnosis among adults with DS.

Biomarkers.

Background: Adults with Down syndrome (DS) overproduce amyloid precursor protein, develop amyloid plaques at an early age, and are diagnosed with Alzheimer's disease (AD) dementia at a high frequency. There is emerging evidence that cerebrovascular disease is elevated across the AD continuum in older adults with DS, independent of age and vascular risk, around the same time as amyloid and tau, but the regional rates of accumulation within individuals are unknown.

Method: Adults with DS from the multisite Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n=78; age=50±6; 40% women) have two timepoints of T2 FLAIR MRI (1.

Biomarkers.

Background: Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) are the predominant types of dementia in older adults, associated with memory loss and cognitive deficits. White matter hyperintensities (WMH) are linked to both AD and VCID. Astrocytes play a crucial role in WM integrity, encompassing functions like neuroinflammation, oxidative stress, and Aβ clearance.