Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with the repeated microtubule-binding domains of three (3R) or four (4R) repeats. Under normal conditions, the 4R:3R ratio is 1:1. In PSP, the 4R isoform is predominantly expressed. The lesions in PSP brains are phosphorylated tau aggregates in both neurons and glial cells. These neurodegenerative diseases with abnormal tau inclusions are called tauopathies, including Alzheimer’s disease (AD). AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. Objective: Our objective was to evaluate and compare the pathological tau processing in PSP and AD. Methods: Double and triple immunofluorescence with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) were carried out and analyzed by confocal microscopy. Results: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Truncated tau at Glu391 and Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR and the absence of intact or phosphorylated tau. Conclusion: Phosphorylated tau was abundantly evidenced in PSP as in AD. The presence of eNFTs in glial cells and neuronal bodies suggest that other truncated tau species different from those observed in AD could be present in PSP. Additional studies on truncated tau within PSP lesions could improve understanding of tau’s pathological processing and help identify a discriminatory biomarker for AD and PSP.

Amyloidosis is a pathological condition which consists on the accumulation of fibrillar proteins. This disease is characterized by extracellular amyloid deposits with a clinical variability depending on the affected tissue. Histopathological evidence indicates that diabetes mellitus type 2 (DM2) induces dementia development, specifically Alzheimer's disease (AD). It has been demonstrated in animal subjects that there is a possibility that aberrant signaling of insulin is a key factor in the induction of the pathology of AD. Recently, there has been newly emerged evidence regarding the relationship between the pathogenesis of Parkinson's disease (PD) and insulin resistance. On another note, the importance of the amyloid deposits in the patients' pancreas with DM2 was evidenced by the discovery of islets of amyloid polypeptide. This has generated interest in the search of the etiopathogenic role of DM2 in the carbohydrates' metabolism. Finally, it is important to consider DM2 as a risk factor essential for the formation of deposits of amyloid-β in patients' brains with dementia.