Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains

Abstract

In a constantly aging population, the prevalence of neurodegenerative disorders is expected to rise. Understanding disease mechanisms is the key to find preventive and curative measures. The most effective way to achieve this is through direct examination of diseased and healthy brain tissue. The authors present a protocol to obtain, process, characterize and store good quality brain tissue donated by individuals registered in an antemortem brain donation program. The donation program includes a face-to-face empathic approach to people, a collection of complementary clinical, biological, social and lifestyle information and serial multi-dimensional assessments over time to track individual trajectories of normal aging and cognitive decline. Since many neurological diseases are asymmetrical, our brain bank offers a unique protocol for slicing fresh specimens. Brain sections of both hemispheres are alternately frozen (at-80 °C) or fixed in formalin; a fixed slice on one hemisphere corresponds to a frozen one on the other hemisphere. With this approach, a complete histological characterization of all frozen material can be obtained, and omics studies can be performed on histologically well-defined tissues from both hemispheres thus offering a more complete assessment of neurodegenerative disease mechanisms. Correct and definite diagnosis of these diseases can only be achieved by combining the clinical syndrome with the neuropathological evaluation, which often adds important etiological clues necessary to interpret the pathogenesis. This method can be time consuming, expensive and limited as it only covers a limited geographical area. Regardless of its limitations, the high degree of characterization it provides can be rewarding. Our ultimate goal is to establish the first Italian Brain Bank, all the while emphasizing the importance of neuropathologically verified epidemiological studies. 3. Meanwhile in the USA, Wallace Tourtelotte introduced antemortem brain donation programs to facilitate solicitation of

Expression pattern of perilipins in human brain during aging and in Alzheimer's disease

“…From all these samples, the following brain areas were studied: frontal and temporal cortex, cerebellum and hippocampus. All donors underwent an extensive multidimensional assessment including clinical diagnosis, neuropsychological, biological and social evaluations, as previously described [ 31 , 32 ]. The study protocol received approval from the Ethical Committee of Pavia University (Committee report 3/2009).…”

Differential Neuropathology, Genetics, and Transcriptomics in Two Kindred Cases with Alzheimer’s Disease and Lewy Body Dementia

“…All clinical assessments were performed by the same team (neurologists, geriatricians and neuropsychologists), according to the Abbiategrasso Brain Bank protocol (ABB) [47]. The ABB autopsy and sampling protocol was approved by the Ethics Committee of the University of Pavia on October 6th, 2009 (Committee report 3/2009).…”

“…Immediately post-mortem, the cerebral hemispheres of the three individuals were harvested following the procedure published in Poloni et al, 2020 [47]. Brie y, the hemispheres were directly fresh-cut in slices alternately frozen (at -80°C) or xed in 10% phosphate-buffered formalin solution for about 5 days.…”

Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

“…Indeed, an Aβ load induces neurodegeneration not per se but through soluble oligomers that disturb cellular functioning through a harmful interaction with the membrane of neurons, especially at the synaptic level. One of the most investigated mechanisms of damage to the neuronal membrane is the possible aggregation of some oligomers (e.g., β [25][26][27][28][29][30][31][32][33][34][35] ) to form anomalous ion channels (increasing the entry of Ca 2+ ) or even real "pores", which can allow the chaotic entry of ions and harmful substances into the neuron [5,6]. All of these detrimental perturbations may induce synaptic dysfunction.…”

“…Current therapies for AD can be stratified according to the stage of the disease that identifies the following three levels of intervention: (1) early prevention of risk factors and lifestyle; (2) disease-modifying treatments (a reduction in the load of Aβ and toxic oligomers, the containment of the phosphorylation of TAU and toxic species of pTAU, the control of neuroinflammation, and an improvement of neuronal resilience); and (3) late symptomatic therapies (the modulation of neurotransmitters and an improvement in synaptic efficiency) [32]. However, many senile cases of AD clearly have mixed conditions of brain pathology [33] and, in the extreme stages of senility, it becomes unrealistic to halt neurodegeneration. In this context, purinergic receptors, especially in the hippocampus, constitute a new and interesting target for modulating and improving synaptic activity, and obtaining symptomatic, and possibly disease-modifying, effects.…”