Spatial transcriptomic patterns underlying amyloid-β and tau pathology are associated with cognitive dysfunction in Alzheimer's disease.

Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts.

Spatial transcriptomic patterns underlying regional vulnerability to amyloid-β and tau pathologies and their relationships to cognitive dysfunction in Alzheimer's disease.

Unlabelled: Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We studied the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies leveraging two large independent cohorts (n = 715) of participants along the AD continuum.

Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer's Disease.

Background: The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina.

Objective: To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline.

Methods: 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD).

Head injury is associated with tau deposition on PET in MCI and AD patients.

Introduction: Head injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important.

Methods: Cognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study.

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years.

Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease.

Identify a global resting-state functional connectivity (gFC) signature in mutation carriers (MC) from the Dominantly Inherited Alzheimer Network (DIAN). Assess the gFC with regard to amyloid (A), tau (T), and neurodegeneration (N) biomarkers, and estimated years to symptom onset (EYO). Cross-sectional measures were assessed in MC ( = 171) and mutation noncarrier (NC) ( = 70) participants.

A novel SNCA E83Q mutation in a case of dementia with Lewy bodies and atypical frontotemporal lobar degeneration.

In this case report, we discuss a patient presenting with parkinsonism followed by a non-amnestic dementia with aphasic clinical features, as well as frontal dysexecutive syndrome. There was a family history of dementia with an autopsy diagnosis of "Pick's disease" in the proband's father. Neuroimaging of the patient revealed focal and severe temporal lobe and lesser frontoparietal lobe atrophy.

Visual contrast sensitivity is associated with the presence of cerebral amyloid and tau deposition.

Visual deficits are common in neurodegenerative diseases including Alzheimer's disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer's disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer's disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity.

Every hit matters: White matter diffusivity changes in high school football athletes are correlated with repetitive head acceleration event exposure.

Recent evidence of short-term alterations in brain physiology associated with repeated exposure to moderate intensity subconcussive head acceleration events (HAEs), prompts the question whether these alterations represent an underlying neural injury. A retrospective analysis combining counts of experienced HAEs and longitudinal diffusion-weighted imaging explored whether greater exposure to incident mechanical forces was associated with traditional diffusion-based measures of neural injury-reduced fractional anisotropy (FA) and increased mean diffusivity (MD). Brains of high school athletes (N = 61) participating in American football exhibited greater spatial extents (or volumes) experiencing substantial changes (increases and decreases) in both FA and MD than brains of peers who do not participate in collision-based sports (N = 15).

Tau PET in autosomal dominant Alzheimer's disease: relationship with cognition, dementia and other biomarkers.

Tauopathy is a hallmark pathology of Alzheimer's disease with a strong relationship with cognitive impairment. As such, understanding tau may be a key to clinical interventions. In vivo tauopathy has been measured using cerebrospinal fluid assays, but these do not provide information about where pathology is in the brain.

A Review of Dementia with Lewy Bodies' Impact, Diagnostic Criteria and Treatment.

Dementia with Lewy bodies is one of the most common causes of dementia. It is not as common as Alzheimer's disease; the general public's awareness of the disease is poor in comparison. Its effects on caregivers and patients alike are not well known to the general population.

Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging.

Introduction: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET).

Methods: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch.

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials.

In vivo imaging of the tau protein has the potential to aid in quantitative diagnosis of Alzheimer's disease, corroborate or dispute the amyloid hypothesis, and demonstrate biomarker engagement in clinical drug trials. A host of tau positron emission tomography agents have been designed, validated, and tested in humans. Several agents have characteristics approaching the ideal imaging tracer with some limitations, primarily regarding off-target binding.

Journal Club: comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology.

Advances in neuroimaging, biomarkers, and clinical data have led to the hypothesis that the pathologic process of Alzheimer dementia begins decades prior to functional decline and diagnosis. High-profile clinical trial results have shown that biomarker changes can be made via pharmacologic intervention; however, the timing of this intervention has likely been too late to impact the cascade of neurodegenerative changes. In “Comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology” by Monsell et al.

Immunotherapy for Alzheimer's disease.

The immune system plays a significant role in Alzheimer disease (AD). β-Amyloid deposition in the cortex is thought to be an initiating event in AD and the widely believed amyloid hypothesis proposes removal of amyloid may delay disease progression. Human trials of active or passive immune agents have failed to show benefit and increased adverse events of vasogenic edema and microhemorrhages.

A case of natalizumab-associated progressive multifocal leukoencephalopathy with repeated negative CSF JCV testing.

The development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab is a well-known potential risk. Diagnosis of PML can be confounded in patients with multiple sclerosis (MS) if new demyelinating lesions develop, and the sensitivity of existing diagnostic tests is less than ideal. In the case presented here, four samples of cerebrospinal fluid tested negative for John Cunningham virus (JCV) DNA by polymerase chain reaction, yet brain biopsy eventually proved positive by immunohistochemistry.

Intra-arterial thrombolysis as an ideal treatment for inflammatory bowel disease related thromboembolic stroke: a case report and review.

Thromboembolism, both venous and arterial, is a well-known complication of inflammatory bowel disease, with the risk of stroke highest when patients are less than 50 years of age. Because inflammatory bowel disease patients often have gastrointestinal bleeding, it is a challenge to treat their thromboembolic events with systemic therapy. In this case, a 42-year-old woman with Crohn's disease developed a thromboembolism in her middle cerebral artery and was successfully treated with local intra-arterial thrombolysis.

American childhood football as a possible risk factor for cerebral infarction.

Three adolescent football players who had ischemic stroke associated with football practice and play are described. The literature on stroke associated with childhood sports and football in particular is reviewed, and the multiple mechanisms by which football can contribute to ischemic stroke are discussed.

Simulation of human respiration in fMRI with a mechanical model.

Obtaining functional magnetic resonance images of the brain is a challenging measurement process having a low characteristic signal-to-noise ratio. Images contain various forms of noise, including those induced by physiologic processes. One of the prevalent disturbances is hypothesized to result from susceptibility fluctuations caused by abdominal volume changes during respiration.