Alzheimer & Parkinson

The spread of tau pathology across the cerebral cortex is closely tied to cognitive decline in Alzheimer's disease (AD). To investigate mechanisms underlying tau spread, we measured bioactivity of tau seeds from inferior temporal gyrus (ITG) and superior frontal gyrus (SFG) synaptosomes in 128 individuals and demonstrated that tau seed bioactivity associates with tau phosphorylation, neurofibrillary tangles (NFTs), and cognitive impairment. Incorporating genotype data from the same individuals...

Alzheimer's disease (AD) is an escalating public health concern in low- and middle-income countries like Pakistan, with rising prevalence among the aging population. While global research has increasingly addressed the psychological dimensions of AD, Pakistan's contribution remains limited. This systematic review, conducted in accordance with PRISMA guidelines, examines the scope and focus of psychological research on AD in Pakistan. Eleven empirical studies published between 2014 and 2025 were...

Alzheimer's disease is a progressive neurodegenerative disorder, and the most common cause of dementia, which causes 60 to 70 percent of the cases worldwide, and its prevalence is increasing by more than 55 million people globally, with an expected increase of 139 million cases by 2050. AD is characterized by Amyloid-β plaque deposition, tau hyperphosphorylation, synaptic dysfunction, neuroinflammation, and oxidative stress, which makes the pathophysiology multifactorial and complex in terms of...

The aging brain is highly vulnerable to oxidative genomic damage, the accumulation of which is a hallmark of Alzheimer's disease (AD). The base excision repair (BER) pathway, initiated by DNA glycosylases, serves as the primary guardian against such damage. This review synthesizes recent evidence revealing the dual and dynamic roles of key DNA glycosylases including OGG1, MUTYH, MPG, and members of the NEIL family in AD pathogenesis. Beyond canonical repair functions, these enzymes actively...

Current clinical assessments of Parkinson's disease rely largely on functional scales, which lack sensitivity to subtle muscle alterations. Therefore, developing objective and quantitative tools to support both diagnosis and disease monitoring is needed. Quantitative ultrasound radiofrequency imaging, particularly through Nakagami analysis, offers a non-invasive means of characterizing tissue scattering properties that may reflect Parkinson's disease - related effects. This study aimed to assess...

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To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models...

The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is...

Tauopathies, such as Alzheimer's disease and frontotemporal dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of tau. Molecular mechanisms underlying tauopathies are still poorly understood, which is in part due to a lack of human models autonomously developing major disease hallmarks. The formation of late-stage disease phenotypes may require adult tau isoform expression, which contributes to tau pathogenesis but is challenging to...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, neuroinflammation, and synaptic loss. Existing therapies provide only modest symptomatic relief and fail to slow disease progression. Beyond its role in promoting pituitary growth hormone (GH) secretion, growth hormone-releasing hormone (GHRH) has shown neuroprotective effects in experimental ischemic stroke and spinal muscular atrophy. Here, we explored...

With elderly populations increasing in many countries, rates of Alzheimer disease and related dementias (ADRD) are expected to rise worldwide in the coming years. Low-income and middle-income countries, where barriers to health care are most pronounced and research representation is limited, are predicted to experience the greatest increases in ADRD prevalence. Access to advanced diagnostic and research tools, such as neuroimaging, is severely restricted in these regions, but low-field MRI is...

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Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic...

The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal...

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This article aims to comprehensively analyze the vascular factors in Alzheimer's Disease (AD), particularly the changes in the carotid arteries, and their complex correlations with hippocampal atrophy and cognitive function. Besides the traditional β-amyloid protein (Aβ) and Tau protein hypotheses, vascular factors are increasingly regarded as crucial factors in the development of AD. This article systematically reviews the roles of cerebral blood flow perfusion changes and micro-infarctions in...

The accumulation of amyloid β (Aβ) protein in the brain is a central pathological hallmark of Alzheimer's disease (AD). This process has become a major focus of interdisciplinary research and a critical target in drug development. Aβ is produced through the proteolytic processing of amyloid precursor protein (APP) by a group of enzymes known as secretases. They belong to different protease classes and operate through proteolytic cleavage of the peptide bond through several catalytic hydrolysis....

The core pathological hallmark of Parkinson's disease (PD) is the progressive degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc), driven by misfolding and aggregation of a-synuclein (aSyn) into Lewy bodies. This triggers severe cellular dysfunction, including endoplasmic reticulum (ER) stress and the dysregulation of the unfolded protein response (UPR). TMBIM6, an anti-apoptotic ER protein, inhibits the UPR sensor IRE1a. Although TMBIM6 exhibits...

The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer's disease,...

Despite advances in understanding the mechanisms, risk factors and treatment strategies for Alzheimer's disease (AD), no approved therapies exist to prevent or delay onset in at-risk individuals or those with elevated biomarkers who do not yet show symptoms. Multiple candidate interventions are now being evaluated in clinical trials in these settings, raising key questions around which populations are most appropriate and what criteria should guide regulatory and clinical decision-making. Data...