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Bioinformatics of the Brain

neuroimaging are used for diagnosis, significant findings are usually obtained

in the late stages. Finding robust biomarkers is essential for early-stage di-

agnosis and effective treatment protocol. The first studies focused mostly on

these two molecular pathological processes that result in neuron loss. How-

ever, the lack of an effective treatment protocol yet has increased the number

of studies aimed at elucidating the molecular changes that direct the patho-

genesis of the disease and finding new biomarkers.

While AD studies conducted in recent years offer new perspectives on AD

using various omics approaches, there is great interest in proteomic approaches

that comprehensively reveal pathogenesis-related protein differences [32, 33].

Redox and organelle proteomics have revealed the dysregulation of a num-

ber of proteins related to oxidative stress, impaired energy metabolism, and

mitochondrial and synaptic dysfunctions that occur in the neurodegenerative

process [34–38].

In fact, there are many studies aimed at identifying AD-specific mark-

ers in brain tissue and CSF. Due to the heterogeneous nature of the brain,

some studies have focused on specific brain regions or specific cell populations

and used localized proteomics approaches [39–42]. Frontal cortex and Hip-

pocampus are the regions of the brain most affected by AD. A recent study

examining brain regions affected early (entorhinal and parahippocampal cor-

tices) and late (temporal and frontal cortices) by tau pathology showed that

synaptic proteins are altered in the early B/B stages, whereas proteins in-

dicating translation dysregulation are mainly down-regulated in the frontal,

entorhinal, and parahippocampal cortices [40]. Sathe et al. conducted both

exploratory and targeted proteomic analyses between post-mortem patients

with AD and cognitively normal and age-matched individuals. Using TMT

labeling, researchers identified 8066 proteins in medial frontal gyrus tissues,

432 of which showed significant changes [41]. In another proteomic study con-

ducted on fresh frozen brain tissue samples from the dorsolateral prefrontal

cortex, more than six thousand proteins were identified using prefractionation

and TMT labeling methods, and it was reported that there were changes in

350 proteins, including RNA-binding proteins, between AD and asymptomatic

AD [43].

On the other hand, as an alternative to fresh human tissue, FFPE

(formalin-fixed, paraffin-embedded) tissue may be a valuable source of in-

formation for clinical proteomic studies. Since it can be stored for a long time,

it can also provide the opportunity to evaluate AD patients retrospectively.

Drummond et al. reported a strategy that would be advantageous in eval-

uating very specific cell types in brain regions in their study in which they

isolated neuronal cells from temporal cortex FFPE tissue blocks of patients

with severe AD using the laser capture microdissection (LCM) method [44].

The same researcher also used the LCM method, which allows localized pro-

teomics , for the isolation of amyloid plaques and neurofibrillary tangles [45].

Another study used LCM to compare the amyloid pathology of Rapidly pro-

gressive Alzheimer’s disease (rpAD) and sporadic Alzheimer’s disease (sAD)