Publications by authors named "Lasse S Madsen"
Introduction: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.
Methods: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent C-PK11195 and C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up.
Article Synopsis
- The peripheral immune system influences neurodegenerative diseases like Alzheimer's by both protecting the brain and causing inflammation; however, the exact mechanisms are not fully understood.
- Researchers found large Aβ aggregates in the plasma of patients with mild cognitive impairment, which are linked to early signs of Alzheimer's pathology and a decrease in certain monocytes.
- The study identifies complement receptor 4 as a key player in interacting with amyloids, enhancing phagocytosis and lysosomal activity in microglia, and suggests that Aβ aggregates may help recruit immune cells into the brain, affecting the disease process.
Introduction: Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals.
Methods: Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers.
The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta-amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2-3 times and is associated with earlier Aβ accumulation.
View Article and Find Full Text PDFCardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction.
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- Cerebral perfusion changes are increasingly linked to Alzheimer's disease (AD), with issues in brain microvascular circulation leading to local oxygen shortages.
- The study involved 19 individuals with mild cognitive impairment and high amyloid-β load, finding that these patients exhibited lower microvascular blood flow and more variability in blood transit times compared to those without AD signs and healthy controls.
- A strong correlation was found between high amyloid-β levels and reduced blood flow in specific brain areas, suggesting a harmful cycle where increased amyloid-β and poor blood circulation might worsen each other in the early stages of AD.
Background: The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease.
Methods: Forty-three subjects with mild cognitive impairment (MCI) had serial C-PK11195 PET over 2 years to measure inflammation changes, and C-PiB PET to determine β-amyloid fibril load; 22 also had serial F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years.
Background: Plasma and cerebrospinal fluid levels of neurofilament light (NfL), a marker of axonal degeneration, have previously been reported to be raised in patients with clinically diagnosed Alzheimer's disease (AD). Activated microglia, an intrinsic inflammatory response to brain lesions, are also known to be present in a majority of Alzheimer or mild cognitive impaired (MCI) subjects with raised β-amyloid load on their positron emission tomography (PET) imaging. It is now considered that the earliest phase of inflammation may be protective to the brain, removing amyloid plaques and remodelling synapses.
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