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Advanced Neurology Genomic insights into Alzheimer

and reliability of different studies across varying evidence French (86975.31 Da), and A673V (86971.3) mutations
levels. Given that many of the mutations under study had a (Table 1). The theoretical pI, determining a protein’s acidicity
low number of recorded cases, case reports, and case series or basicity, was consistent among the wild-type APP and
were considered for certain mutations, contingent on the several mutations, including Flemish, A673V, Iranian,
quality of methodology and reported results. However, Austrian, German, French, Iberian, Indiana, V717G,
preference was given to higher-level studies, including London, V717L, T719N, and Australian, all sharing a pI
systematic reviews and case series. Given the nature of the value of 4.73. Notably, the Taiwanese mutation exhibited the
collated data, most studies were of a quantitative nature. highest pI (4.76), while the Swedish mutation displayed the
The results were subsequently summarized in table format lowest pI (4.72). Conversely, the Tottori, Osaka, Arctic, and
for detailed analysis and inclusion in the report. Iowa mutations had a pI of 4.74, surpassing the threshold
value of the wild-type APP (4.73) (Table 1).
3. Results
The AI serves as an indicator of a protein’s
3.1. Analysis of physicochemical properties of the thermostability. Analysis of the AI revealed that both wild-
wild-type and mutated human APP sequences type and mutated APPs generally exhibit thermostability.
The analysis of physicochemical properties for the wild- Notably, the Tottori, Arctic, Iowa, Taiwanese, T719N,
type human and 20 mutated APP, conducted through the and M722K mutations share an identical AI value of
ExPASy ProtParam server, demonstrated variable MW for 73.18, similar to the wild-type APP. Comparatively, when
the mutated APPs compared to the wild-type APP. Herein, assessed against the resultant threshold value, the AI value
significant changes in MW were observed for the Osaka increased for the Austrian and Swedish mutations to 73.69,
(86814.13 Da) and Arctic (86871.19) mutations when followed by A673V (73.43). On the other hand, the AI

compared to the wild-type APP (86943.25) (Table 1). On value decreased for the German (72.94), French, Indiana,
the other hand, the Indiana mutation exhibited the highest V717G (72.81), Iberian, and Australian mutations (72.68)
MW (86991.29 Da), followed by the Iberian (86977.27 Da), when compared to the wild-type APP (Table 1).

Table 1. Physicochemical properties of the wild‑type and 20 mutated human amyloid precursor protein
Mutation MW Theoretical pI II AI GRAVY
Wild-type APP 86943.25 4.73 40.69 73.18 −0.584
A673V 86971.30 4.73 40.69 73.43 −0.581
D678N (Tottori) 86942.26 4.74 40.75 73.18 −0.584
E693∆ (Osaka) 86814.13 4.74 40.37 73.28 −0.580
E693G (Arctic) 86871.19 4.74 40.44 73.18 −0.580
D694N (Iowa) 86942.26 4.74 40.44 73.18 −0.584
A692G (Flemish) 86929.22 4.73 40.59 73.05 −0.587
KM670/671NL (Swedish) 86911.15 4.72 40.31 73.69 −0.581
D678H (Taiwanese) 86965.30 4.76 40.44 73.18 −0.584
T714A (Iranian) 86913.22 4.73 40.69 73.31 −0.581
T714I (Austrian) 86955.30 4.73 40.58 73.69 −0.577
V715A (German) 86915.20 4.73 40.69 72.94 −0.587
V715M (French) 86975.31 4.73 40.69 72.81 −0.587
I716F (Iberian) 86977.27 4.73 40.80 72.68 −0.586
V717F (Indiana) 86991.29 4.73 40.80 72.81 −0.586
V717G 86901.17 4.73 40.69 72.81 −0.590
V717I (London) 86957.28 4.73 40.80 73.31 −0.584
V717L 86957.28 4.73 41.05 73.31 −0.584
T719N 86956.25 4.73 40.69 73.18 −0.588
M722K 86940.23 4.75 40.54 73.18 −0.591
L723P (Australian) 86927.21 4.73 41.37 72.68 −0.591
Abbreviations: AI: Aliphatic index; GRAVY: Grand average hydropathy; II: Instability index; MW: Molecular weight; pI: Theoretical isoelectric point.

Volume 2 Issue 4 (2023) 6 https://doi.org/10.36922/an.1734