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1.
Alzheimers Dement ; 20(2): 1421-1435, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897797

RESUMO

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid ß (Aß) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.


Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Transtornos Cerebrovasculares , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Líquido Extracelular , Angiopatia Amiloide Cerebral/terapia , Angiopatia Amiloide Cerebral/patologia , Encéfalo/metabolismo , Transtornos Cerebrovasculares/complicações
2.
Nat Med ; 20(4): 415-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24608097

RESUMO

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-ß levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.


Assuntos
Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Fosfolipídeos/sangue , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Asparagina/sangue , Biomarcadores , Carnitina/sangue , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Estudos de Coortes , Dipeptídeos/sangue , Feminino , Humanos , Estudos Longitudinais , Lisofosfatidilcolinas/sangue , Malatos/sangue , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Metaboloma , Testes Neuropsicológicos , Fosfatidilcolinas/sangue , Fosfatidilinositóis/sangue , Prolina/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Esfingomielinas/sangue , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/sangue
4.
Clin Chem ; 48(8): 1344-51, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12142393

RESUMO

BACKGROUND: Assays for rearrangement of the immunoglobulin, T-cell receptor, bcr/abl, and bcl-2 genes are valuable tools to aid in the diagnosis of leukemias and lymphomas and are now offered by many pathology laboratories. However, there is a lack of well-characterized and validated calibrators and positive controls for these assays. We therefore evaluated 16 readily available leukemia and lymphoma cell lines for their potential use as controls. METHODS: DNA and RNA were isolated from each cell line and analyzed by Southern blot and PCR or reverse transcription-PCR (RT-PCR). Rearrangements in the IgJ(H), IgJ(kappa), TcR-beta or TcR-gamma, bcr/abl, and bcl-2 genes were detected by commercially available probes and primers. Cell lineages were confirmed by immunophenotyping. RESULTS: Immunoglobulin and T-cell receptor gene rearrangements were identified in five B- and three T-cell lines, respectively. Two cell lines tested positive for the bcr/abl gene, and one was positive for the bcl-2 gene rearrangement by Southern blot. CONCLUSIONS: The 16 cell lines studied can be used as positive controls in molecular detection assays for gene rearrangements. The parallel processing of these cell lines with clinical samples can serve to quality control the experimental procedures from the first step of DNA or RNA extraction to the final step of result analysis.


Assuntos
Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Leucemia/patologia , Linfoma/patologia , Células Tumorais Cultivadas , Linfócitos B/metabolismo , Southern Blotting , Citometria de Fluxo , Proteínas de Fusão bcr-abl/genética , Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Genes bcl-2 , Humanos , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Imunofenotipagem , Reação em Cadeia da Polimerase , Linfócitos T/metabolismo
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