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Avanços na dinâmica epidemiológica e identificação de biomarcadores na doença de Alzheimer
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Advisor(s)
Abstract(s)
A Doença de Alzheimer (DA) é a forma mais comum da demência, com um número crescente de casos diagnosticados anualmente. Trata-se de uma patologia neurodegenerativa crónica e progressiva, que afeta sobretudo indivíduos em idade avançada, embora possam ocorrer casos precoces, a partir dos 45 anos. O depósito do péptido β-amiloide (βA) e a hiperfosforilação da proteína Tau nos neurónios levam à atrofia do córtex cerebral, resultando em perda sináptica e
morte neuronal. Esta degeneração culmina na perda das funções cognitivas, afetando principalmente a memória.
O presente estudo tem como objetivo analisar a dinâmica epidemiológica da DA e outras demências entre 1990 e 2021, focando-se nas regiões da Europa Ocidental e da África Subsariana Ocidental, com especial atenção a Portugal e Cabo Verde. Para isso, foram analisadas as medidas de prevalência, incidência, DALYs (Disability- Adjusted Life Years) e mortalidade padronizadas por idade, com base nos dados do Estudo de Carga Global de Doenças, Lesões e Fatores de Risco (GBD). Foram comparados os padrões epidemiológicos entres as regiões e os dois países e
identificados biomarcadores utilizados no diagnóstico da DA, incluindo novos métodos
promissores.
Os resultados indicam que a incidência, prevalência, DALYs e mortalidade da DA e outras demências se mantiveram estáveis ao longo do tempo, com taxas mais elevadas na Europa Ocidental e em Portugal devido ao maior envelhecimento da população e ao melhor acesso ao diagnóstico. Em ambas as regiões e países, o sexo feminino apresentou taxas superiores às do sexo masculino, refletindo a maior longevidade.
Para a identificação de biomarcadores, foi realizada uma revisão da literatura recente (últimos 15 anos) em língua inglesa, através da base de dados PubMed. A análise de biomarcadores neuro-químicos, a partir de amostras do líquido cefalorraquidiano (LCR) inclui os agregados de βA (βA1-40 e βA1-42), a proteína Tau fosforilada (P-Tau) em relação à Tau Total (T-Tau), a neurogranina e os Neurofilamentos de Cadeia Leve (NFL). Estes marcadores também
podem ser detetados no sangue, embora em níveis mais baixos. Outros biomarcadores relevantes incluem os estruturais e funcionais, como o Fluorodeoxiglicose (FDG-PET), PET-Amiloide e Tau PET, recorrendo a técnicas de imagem de alta resolução.
Apesar dos avanços, continua a ser necessário desenvolver métodos de diagnostico mais fiáveis, acessíveis e menos invasivos que permitam um diagnostico precoce de DA e a sua diferenciação de outras doenças neurodegenerativas. Estas melhorias são essenciais para possibilitar intervenções terapêuticas mais eficazes e para mitigar o impacto crescente da doença na população.
Alzheimer's Disease (AD) is the most common form of dementia, with a growing number of cases diagnosed annually. It is a chronic and progressive neurodegenerative disorder that primarily affects elderly individuals, although early-onset cases can occur from the age of 45. The deposition of β-amyloid (βA) peptide and the hyperphosphorylation of Tau protein in neurons lead to cortical atrophy, resulting in synaptic loss and neuronal death. This degeneration culminates in the loss of cognitive functions, primarily affecting memory. The present study aims to analyze the epidemiological dynamics of AD and other dementias between 1990 and 2021, focusing on the regions of Western Europe and Western SubSaharan Africa, with particular attention to Portugal and Cape Verde. To achieve this, age standardized indicators of prevalence, incidence, Disability-Adjusted Life Years (DALYs), and mortality were analyzed, based on data from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD). Epidemiological patterns between the regions and the two countries were compared, and biomarkers used in the diagnosis of AD, including promising new methods, were identified. The results indicate that the incidence, prevalence, DALYs, and mortality rates of AD and other dementias remained stable over time, with higher rates in Western Europe and Portugal due to the aging population and better access to diagnosis. In both regions and countries, females showed higher rates than males, reflecting greater longevity. To identify biomarkers, a review of recent literature (from the past 15 years) in English was conducted using the PubMed database. The analysis of neurochemical biomarkers from cerebrospinal fluid (CSF) samples includes βA aggregates (βA1-40 and βA1-42), phosphorylated Tau protein (P-Tau) relative to Total Tau (T-Tau), neurogranin, and Neurofilaments of Light Chain (NFL). These markers can also be detected in blood, albeit at lower levels. Other relevant biomarkers include structural and functional markers, such as Fluorodeoxyglucose (FDG-PET), Amyloid-PET, and Tau-PET, using high-resolution imaging techniques. Despite advancements, further research is needed to develop more reliable, accessible, and less invasive diagnostic methods that enable early detection of AD and its differentiation from other neurodegenerative diseases. These improvements are essential for enabling more effective therapeutic interventions and mitigating the growing impact of the disease on the population.
Alzheimer's Disease (AD) is the most common form of dementia, with a growing number of cases diagnosed annually. It is a chronic and progressive neurodegenerative disorder that primarily affects elderly individuals, although early-onset cases can occur from the age of 45. The deposition of β-amyloid (βA) peptide and the hyperphosphorylation of Tau protein in neurons lead to cortical atrophy, resulting in synaptic loss and neuronal death. This degeneration culminates in the loss of cognitive functions, primarily affecting memory. The present study aims to analyze the epidemiological dynamics of AD and other dementias between 1990 and 2021, focusing on the regions of Western Europe and Western SubSaharan Africa, with particular attention to Portugal and Cape Verde. To achieve this, age standardized indicators of prevalence, incidence, Disability-Adjusted Life Years (DALYs), and mortality were analyzed, based on data from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD). Epidemiological patterns between the regions and the two countries were compared, and biomarkers used in the diagnosis of AD, including promising new methods, were identified. The results indicate that the incidence, prevalence, DALYs, and mortality rates of AD and other dementias remained stable over time, with higher rates in Western Europe and Portugal due to the aging population and better access to diagnosis. In both regions and countries, females showed higher rates than males, reflecting greater longevity. To identify biomarkers, a review of recent literature (from the past 15 years) in English was conducted using the PubMed database. The analysis of neurochemical biomarkers from cerebrospinal fluid (CSF) samples includes βA aggregates (βA1-40 and βA1-42), phosphorylated Tau protein (P-Tau) relative to Total Tau (T-Tau), neurogranin, and Neurofilaments of Light Chain (NFL). These markers can also be detected in blood, albeit at lower levels. Other relevant biomarkers include structural and functional markers, such as Fluorodeoxyglucose (FDG-PET), Amyloid-PET, and Tau-PET, using high-resolution imaging techniques. Despite advancements, further research is needed to develop more reliable, accessible, and less invasive diagnostic methods that enable early detection of AD and its differentiation from other neurodegenerative diseases. These improvements are essential for enabling more effective therapeutic interventions and mitigating the growing impact of the disease on the population.
Description
Tese de mestrado, Ciências Biofarmacêuticas, 2025, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
GBD Doença de Alzheimer Demência Biomarcadores Dinâmica epidemiológica Cabo Verde Portugal Teses de mestrado - 2025