Denser brain capillary network with preserved pericytes in Alzheimer's disease

Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood-brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state-of-the-art stereological morphometry techniques as well as tissue clearing and two-photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non-demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid beta deposition. Two-photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology

Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Glucose hypometabolism potentially contributes to Alzheimer’s disease (AD) and might even represent an underlying mechanism. Here, we investigate the relationship of diet-induced metabolic stress and AD as well as the therapeutic potential of chia seeds as a modulator of glucose metabolism in the APP23 mouse model. 4–6 (pre-plaque stage, PRE) and 28–32 (advanced-plaque stage, ADV) weeks old APP23 and wild type mice received pretreatment for 12 weeks with either sucrose-rich (SRD) or control diet, followed by 8 weeks of chia seed supplementation. Although ADV APP23 mice generally showed functioning glucose homeostasis, they were more prone to SRD-induced glucose intolerance. This was accompanied by elevated corticosterone levels and mild insulin insensitivity. Chia seeds improved spatial learning deficits but not impaired cognitive flexibility, potentially mediated by amelioration of glucose tolerance, attenuation of corticosterone levels and reversal of SRD-induced elevation of pro-inflammatory cytokine levels. Since cognitive symptoms and plaque load were not aggravated by SRD-induced metabolic stress, despite enhanced neuroinflammation in the PRE group, we conclude that impairments of glucose metabolism do not represent an underlying mechanism of AD in this mouse model. Nevertheless, chia seeds might provide therapeutic potential in AD as shown by the amelioration of cognitive symptoms

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon longterm challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1H-magnetic resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis