Amyloidosis

Alzheimer's Disease (AD) is characterized by a range of behavioral alterations, including memory loss and psychiatric symptoms. While there is evidence that molecular pathologies, such as amyloid beta (Aβ), contribute to AD, it remains unclear how this histopathology gives rise to such disparate behavioral deficits. One hypothesis is that Aβ exerts differential effects on neuronal circuits across brain regions, depending on the neurophysiology and connectivity of different areas. To test this, we recorded from large neuronal populations in dorsal CA1 (dCA1) and ventral CA1 (vCA1), two hippocampal areas known to be structurally and functionally diverse, in the APP/PS1 mouse model of amyloidosis...

Amyloidosis is a disease characterized by the deposition of protein fibrils. Cardiac involvement is a significant factor in determining prognosis. This study aimed to examine the clinical profile, outcomes, and long-term mortality rates in patients with transthyretin (ATTR) and amyloid light-chain (AL) amyloidosis. The retrospective cohort study included 94 patients with amyloidosis (69 with AL and 25 with ATTR amyloidosis) diagnosed between 2010 and 2022. The study involved multimodality imaging (ECG, echocardiography and cardiac magnetic resonance (CMR) data and survival analyses...

Amyloidosis involving the lacrimal sac is extremely rare. In this study, we demonstrated a rare case of localized light chain amyloidosis in the lacrimal sac region. The lacrimal sac lesion presented as infiltrative with bony erosion. Given the slow growth of the lesion and the absence of a blood flow signal inside, we concluded that the lesion was less likely to be malignant. Complete removal of the lacrimal sac lesion combined with simultaneous lacrimal passage reconstruction was performed. The diagnosis of light chain amyloidosis was confirmed by histology...

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. Waldenström macroglobulinemia (WM) with systemic amyloidosis as the main manifestation is even rarer. The patient in this study presented with recurrent diarrhea and had not been diagnosed in other hospitals on multiple occasions. Later, his diarrhea worsened and was accompanied by sunken edema of both lower limbs and dizziness. Renal biopsy showed deposits of PAS light-staining material in the glomeruli, interstitium, and small arteries, which stained positively with Congo red...

Alzheimer's disease is classified as a progressive disorder resulting from protein misfolding, also known as proteinopathies. Proteinopathies include synucleinopathies triggered by misfolded amyloid α-synuclein, tauopathies triggered by misfolded tau, and amyloidopathies triggered by misfolded amyloid of which Alzheimer's disease (β-amyloid) is most prevalent. Most neurodegenerative diseases (>90%) are not due to dominantly inherited genetic causes. Instead, it is thought that the risk for disease is a complicated interaction between inherited and environmental risk factors that, with age, drive pathology that ultimately results in neurodegeneration and disease onset...

BACKGROUND: ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR. OBJECTIVES: To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients...

BACKGROUND: We aimed to investigate coronavirus diease 2019 (COVID-19) outcomes in patients with amyloid A protein (AA) amyloidosis secondary to rheumatic diseases and discuss factors associated with disease course. METHODS: A retrospective cohort was formed from adult patients with a diagnosis of AA amyloidosis. In patients with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) test, rates of hospitalization, intensive care unit admission and mortality due to COVID-19 were collected from medical records...

Midlife cerebrovascular risk factors increase risk of late life cognitive impairment and dementia, while their presence in patients with dementia may lead to cognitive improvement or stabilization in late life. Defining the best measure of blood pressure (BP) to be associated with cognitive decline remains debatable, also due to possible bidirectionality. BP variability, pulse pressure, systolic and diastolic BP have been associated with cognitive status, dementia risk and Alzheimer's disease biomarkers. Proper BP control notwithstanding, BP variability increases risk for pathophysiological change in the Alzheimer's disease continuum, implying the need for selection of anti-hypertensive drugs with neurobiological evidence of benefits...

BACKGROUND: Recent evidence suggests that both serum neurofilament light chain (sNfL) levels and small fiber related diagnostic variables may be valuable disease biomarkers of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Our study aimed to explore the relations between sNfL and small fiber related skin biopsy and quantitative sensory testing (QST) parameters in a cohort of ATTRv-PN patients and pre-symptomatic carriers. METHODS: We retrospectively analyzed data from 13 ATTRv patients and 21 pre-symptomatic carriers who underwent sNfL dosage, skin biopsy, and QST, and analyzed correlations between sNFL, intraepidermal nerve fiber density (IENFD), and cold (CDT) and warm detection thresholds (WDT)...

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023...

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels...

Median neuropathy at the wrist, commonly referred to as carpal tunnel syndrome (CTS), is the most common entrapment neuropathy. It is caused by chronic compression of the median nerve at the wrist within the space-limited carpal tunnel. Risk factors that contribute to the etiology of compression include female gender, obesity, work-related factors, and underlying medical conditions, such as hypothyroidism, pregnancy, and amyloidosis. The diagnosis is made on clinical grounds, although these can be confounded by anatomical variations...

BACKGROUND: Amyloid deposition in tenosynovial structures precedes cardiac involvement up to 20 years. Therefore, a cardiological screening in patients with a history of tenosynovial manifestations of cardiac amyloidosis (CA) could lead to an increased number of early diagnoses. METHODS: Patients with tenosynovial manifestations of CA (carpal tunnel syndrome, atraumatic biceps tendon rupture, lumbar spinal stenosis) have been identified by general practitioners and evaluated in a Referral Center for CA...

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OBJECTIVE: To study the severity and localization of dilated perivascular spaces (DPVS), the levels of protein markers of amyloidosis and neurodegeneration in the cerebrospinal fluid (CSF) at different daily blood pressure (BP) profiles in patients with Alzheimer's disease (AD) and other types of cognitive impairment. MATERIAL AND METHODS: A total of 119 people, aged 53 to 92 years, including 55 patients with AD, 27 patients with vascular cognitive disorders (VCD), 19 patients with frontotemporal degeneration (FTD)...

No abstract text is available yet for this article.

Amyloid light-chain (AL) amyloidosis is a rare hematological disease that produces abnormal monoclonal immunoglobulin light chains to form amyloid fibrils that are deposited in tissues, resulting in organ damage and dysfunction. Advanced AL amyloidosis has a very poor prognosis with a high risk of early mortality. The combination of anti-plasma cell therapy and amyloid fibrils clearance is the optimal treatment strategy, which takes into account both symptoms and root causes. However, research on anti-amyloid fibrils lags far behind research on anti-plasma cells, and there is currently no approved treatment that could clear amyloid fibrils...

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease in which extracellular aggregates of the amyloid beta (Aβ) peptide precede widespread intracellular inclusions of the microtubule-associated protein tau. The autosomal dominant form of AD requires mutations that increase production or aggregation of the Aβ peptide. This has led to the hypothesis that amyloid deposition initiates downstream responses that lead to the hyperphosphorylation and aggregation of tau...

INTRODUCTION: Amyloid A amyloidosis of the bladder is not a major disease. We report a patient with systemic amyloid A amyloidosis of the bladder after transurethral resection of urothelial carcinoma. CASE PRESENTATION: An 87-year-old Japanese man had bladder carcinoma. He was followed up regularly with cystoscopy. Cystoscopy revealed multiple polypoid tumors 6 months after the first transurethral resection of urothelial carcinoma. Pathologic specimens contained the amyloid A component...

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50...