
algimers vyaadhi yokka jeevarasaayana shaastram

chittavaikalyaaniki atyanta saadhaarana kaaranam ayina algimers vyaadhi yokka jeevarasaayana shaastram inca baga ardham kaaledu. algimers vyaadhi (AD) oka proteopatigaa gurtinchabadindih medadulo asadhaaranamgaa madathapette amyloid beata (aβ) protein perukupovadam valla protein tappugaa madathapette vyaadhi. amyloid beata anedi oka chinna peptide, idhi transmembrane protein amyloid-beata puurvagaami protein (yap) yokka asaadhaarana proteolytic upa utpatti, dheeni paniteeru aspashtamgaa undhi conny neuronal abhivruddhilo paalgontunnatlu bhaavistaaru. presenilinlu anevi yap prosessing mariyu ksheenatalo palgone proteolytic complexes yokka bhagalu.
amyloid beata monomerlu karigevi mariyu beata sheet mariyu polyproline II helix dviteeya nirmaanaala yokka chinna praantaalanu draavanamloo kaligi untaayi, ayinappatikee avi porallo ekkuvagaa alfa helikalga untaayi; ayithe, taginanta adhika saandratatoe, avi beata sheet-ritch trutheeya nirmaanaanni roopondinchadaaniki naatakeeya conformational maarpuku lonavutaayi, idhi amyloid fibrilsnu yerparustundi. eee fibrills mariyu aβ yokka oligomeric roopaalu neuronla velupala senail plakes anie piluvabade nirmaanaalalo jama avtayi. diffuse", "compact", "coord" ledhaa neuritic plake rakaalato sahaa vividha rakaala falakaalu unnaayi, alaage medadulooni chinna raktanaalaala godalalo aβ niksheepaalu cerebral amyloid angiopathy anie pilustaaru.
tou protein yokka asaadhaarana aggregation kaaranamgaa kooda yaad oka tavopatiga pariganinchabadutundi, idhi neuronlalo vyakteekarinchabadina microtuble-sambandhita protein, idhi saadhaaranamgaa sell cytoskelitanloni microtublesnu sthireekarinchadaaniki panichestundi. chaalaa microtuble-sambandhita proteinla maadirigaane, tou saadhaaranamgaa phosphorylation dwara niyantrinchabadutundi; ayithe, algimers vyaadhiloo, hyperphosphorylated tou jatha cheyabadina helical philamentlugaa perukupotundi, ivi neurofibrillary tangles anie piluvabade naraala kanaala lopala dravyaraasigaa mariyu amyloid phalakaalato anubandhinchabadina dystrophic neuritelugaa kalisipotayi. filament assembly prakriya gurinchi chaalaa takkuva telisinappatikii, parvulin kutumbamlo prolyl isomerase protein ksheenata asaadhaarana tou perukupovadaanni vegavantam chestundani choopabadindi.
sanklishtamaina cascade loe neuro inflammation kooda paalgontundi, idhi prakatana pathology mariyu lakshanaalaku daariteestundi. raktam mariyu cerebrospinal dravam loe perigina shotha nirodhaka cytokine saandratalatoe sahaa, prakatanatho sambandham unna roganirodhaka maarpulanu gananeeyamaina rogalakshana mariyu clinical aadharalu namodu chestaayi. eee maarpulu prakatanaku kaaranam ledhaa paryavasanamga undavachaa anedi puurtigaa ardham chesukovalasi undhi, conny medadulooni vaapu, amyloid nikshepaala patla resident microglia yokka perigina reactivitytho sahaa, vyadhikaaraka mariyu prakatana yokka purogati loe chikkukundi. algimers vyaadhi yokka prayogaatmaka namuunaalanu upayoginchi parisoedhana dwara algimers vyaadhi yokka telisina jeevarasaayana shaastram chaalaa varaku ardham cheyabadindi.
neuropathology.
sthuuladarshini sthaayilo, mastishka valkalam mariyu konni upa-cartical praantaalalo neuronlu mariyu synapses kolpovadam dwara AD vargeekarinchabadutundi. idhi prabhaavita praantaala sthuula ksheenataku daariteestundi, indulo taatkaalika lobe mariyu parial lobe loe ksheenata, mariyu mundu valkalam mariyu singulate gyrus yokka bhagalu untaayi.
prakatana medadullo suukshmadarshini dwara amyloid falakaalu mariyu neurofibrillary chikkulu rendoo spashtamgaa kanipistaayi. falakaalu dattamainavi, ekkuvagaa neuronla velupala mariyu chuttoo protein mariyu cellular padaartham yokka karagani niksheepaalu. chikkulu anevi naraala kanam lopala erpade karagani vakreekruta fibers. chaalaa mandhi vruddhulu konni falakaalu mariyu chikkulanu abhivruddhi chesinappatiki, prakatana rogula medadulu vaatini chaalaa ekkuvagaa mariyu medadulooni vividha pradaesaalaloo kaligi untaayi.
jeevarasaayana lakshanaalu.
algimers vyaadhini ardham chesukovadaniki praadhamikamainadi amyloid-beata falakaalu mariyu tou-protein chikkulu perukupovadaniki daariteese jeevarasaayana sanghatanalu. enjaimla sraavaala sunnitamaina samatulyata amyloid-beata perukupovadaanni niyantristundi. alfa sraavam anedi naan-pathological (naan-amyloidogenic) amyloid beata (doih 10.2174/156720512799361655) nuu andinchagaladu. iteevala, colinergic neuronal activity mariyu alfa-sraavam yokka kaaryaacharana madhya sambandham highlight cheyabadindi, idhi algimers vyaadhi unna rogula medadulo amyloid-beata proteinla nikshepananu nirutsaahaparustundi. 
algimers vyaadhini protein misfolding vyaadhi ledhaa proteopatigaa gurtinchaaru, idhi prakatana rogula medadullo asadhaaranamgaa madathapette amyloid-beata proteinla perukupovadam valla vastundi. asaadhaarana amyloid-beata perukupovadaanni modata cerebrospinal dravam vislaeshanhanu upayoginchi mariyu taruvaata positron emission tomography (pempudu jantuvu) nuu upayoginchi gurtinchavacchu.
idhi priyan vyaadhulatoe pathophysiological mechanismlanu panchukunnappatiki, idhi priyan vyaadhula vale vyaapinchadu. amyloid-beata, aβ anie kooda vraayabadutundi, idhi oka chinna peptide, idhi transmembrane protein amyloid puurvagaami protein (yap) yokka proteolytic upa utpatti, dheeni paniteeru aspashtamgaa undhi conny neuronal abhivruddhilo paalgontunnatlu bhaavinchabadutundi. presenilinlu anevi yap prosessing mariyu ksheenatalo palgone proteolytic complexes yokka bhagalu.
amyloid beata monomerlu pramaadakaram kaanappatikee, avi beata sheet-ritch trutheeya nirmaanaanni roopondinchadaaniki taginanta adhika saandratatoe naatakeeyamaina nirmaana maarpuku lonavutaayi, ivi amyloid fibrillanu yerparustaayi, ivi neuronla velupala "senail plakes" ledhaa "neuritic plakes" anie piluvabade dattamaina nirmaanaalalo, takkuva dattamaina aggregatelalo "diffuse plakes" gaa, mariyu konnisaarlu medadulooni chinna rakta naalaala godalalo amyloid angiopathy ledhaa congophilic angiopathy anie piluvabade prakriyaloo jama avtayi.
tou protein yokka asaadhaarana aggregation kaaranamgaa kooda yaad oka tavopatiga pariganinchabadutundi, idhi neuronlalo vyakteekarinchabadina microtuble-sambandhita protein, idhi saadhaaranamgaa sell cytoskelitanloni microtublesnu sthireekarinchadaaniki panichestundi. chaalaa microtuble-sambandhita proteinla maadirigaane, tou saadhaaranamgaa phosphorylation dwara niyantrinchabadutundi; ayithe, prakatana rogulalo, hyperphosphorylated tou jatha cheyabadina helical philamentlugaa perukupotundi, ivi "neurofibrillary tangles" anie piluvabade naraala kanaala lopala dravyaraasigaa mariyu amyloid phalakaalato anubandhinchabadina dystrophic neuritelugaa kalisipotayi.
neurotransmitter acetylcholine (eah. sii. hetch) sthaayilu taggutaayi. itara neurotransmitterla serotonin, norpinefrine mariyu somatostatin sthaayilu kooda tarachugaa taggutaayi. anty-collinesterase dwara aach nii tirigi nimpadam anedi eff. dii. yea. chae aamodinchabadina chikitsa vidhanam. grahakam nundi vidipoye raetu nemmadigaa unde synthetic agonistlu m1-m3 rakaala yokka akk grahakalanu prerepinche pratyaamnaaya paddhati algimers vyaadhiloo tadupari taram colinomimeticga pratipaadinchabadindi [15].
vyaadhi yantraamgaalu.
medadulooni prakatana yokka sthuula hystological lakshanaalu baga vargeekarinchabadinappatiki, praathamika kaaranaaniki sambandhinchi aneka vibhina parikalpanalu munduku vachayi. colinergic sankethaalalo lopam vyaadhi purogatini praarambhistundani soochinche colinergic parikalpana atyanta puraatana parikalpanalo okati. kanam lopala tou proteinnu tappugaa madata pettadam mariyu kanam velupala amyloid beata yokka aggregation rendoo prakatana pathologyki daariteese cascadenu praarambhistaayani prastuta siddhaantaalu sthaapistunnaayi. kotta sambhaavya parikalpanalu jeevakriya karakalu, raktanaalaala bhangam mariyu medadulo deerghakaalikamgaa perigina vaapunu prakatanaku dohadapade karakaluga pratipaadistaayi. paramaanu praarambhaaniki sambandhinchina amyloid beata parikalpana eee roeju varaku chaalaa mandhi parisoedhakulaloo prabalamgaa maarindi. amyloid mariyu tou parikalpanalu atyanta vistrutamgaa aamodinchabaddaayi.
tou parikalpana.
tou anedi praadhamika kaaraka karakam anae parikalpana, amyloid phalakaala nikshepana neuron nashtamtho baga sambandham kaligi undadani pariseelanaloo chaalaa kaalamgaa aadhaarapadindi. cytoskeleton ksheenataku daariteese microtuble-sthireekarana tou protein nashtam aadhaaramgaa neurotoxicity kosam oka yantraangam pratipaadinchabadindi. ayithe, tou hyperphosphorylation mundu ledhaa asaadhaarana helical filament aggregates erpadatam valla sambhavistundaa anae daanipai ekaabhipraayam ledhu. tou parikalpanaku maddatu kooda toupathi anie piluvabade itara vyaadhula uniki nundi vachindi, dheenilo adhe protein gurtinchadagina vidhamgaa tappugaa madata pettabadutundi. ayithe, ekkuva mandhi parisoedhakulu amyloid praathamika kaaraka karakamani pratyaamnaaya parikalpanaku maddatu istunnaru.
amyloid parikalpana.
amyloid beata puurvagaami anuvartanam kosam janyuvu chromosome 21loe unnanduna amyloid parikalpana kanugonabadindi, mariyu trisomy 21 unna rogulu-down syndrome anie baga pilustaaru-adanapu janyu coppy unnavaaru 40 samvatsaraala vayassulo prakatana-vanti rugmatalanu pradarsistaaru. amyloid parikalpana paripakva aggregated amyloid fibrills yokka cytotoxicityni suuchistumdi, ivi kana calcium ayan homeostasisnu antaraayam kaliginchadaaniki mariyu apoptosisnu prerepinchadaaniki kaaranamayye protein yokka vishapuurita roopamgaa nammutaaru. fibrilsnu vaegamgaa "inn vitro" gaa yerparuchukune beata amyloid protein yokka adhika sthaayilu munupati prarambham mariyu eluka namoonaalalo ekkuva abhignaa balaheenatatoo mariyu maanavulalo prakatana rooga nirdhaaranatoo sambandham kaligi unnayani pariseelana dwara eee parikalpanaku maddatu labhistundi. ayithe, prerita calcium pravaahaaniki sambandhinchina vidhanalu ledhaa paripakva fibrills dwara pratyaamnaaya cytotoxic vidhaanaala pratipaadanalu spashtamgaa laevu.
amyloid parikalpana yokka iteevali vaividhyam cytotoxic jaatulanu amyloid beata yokka madhyantara tappu madata roopamgaa gurtistundi, karige monomer ledhaa parinati chendina aggregated polymer kaadu, conny oligomeric jaathi, bahusha toroidal ledhaa starr aakaaramlo untundi, idhi sell membrane bhouthikamgaa kuttadam dwara apoptosisnu prerepistundi. eee ayan chaanal parikalpana, karige, naan-fibrillar aβ yokka oligomerlu neuranlaloki aniyantrita calcium pravahanni anumatinche pora ayan chaanellanu yerparustaayani pratipaadistundi. sambandhita pratyaamnaayam, neuronlalo dendritic prakriyalu mariyu oxanlaku sthaanikeekarinchabadina globular oligomer cytotoxic jaathi anie suuchistumdi. prefibrillar aggregatelu poraku antaraayam kaliginchagalavani choopabadindi.
cytotoxic-fibrill parikalpana aushadha abhivruddhiki spashtamaina lakshyanni andistundihi fibrilisation prakriyanu nirodhistundi. seesam sammelanaalapai chaalaa prarambha abhivruddhi pani eee nirodhampai drushti pettindi; chaalaa varaku neurotoxicityni taggistundani kooda nivedinchabadindi, ayithe vishapuurita-oligomer siddhaantam oligomeric assembleeni nivaarinchadam marinta mukhyamaina prakriya anie suuchistumdi.
 ledhaa merugaina lakshyam eguvana undhi, udaaharanaku amyloid beetaaku yap prosessingnu nirodhinchadam. udaaharanaku, morris neeti chittadavi vijayavantamgaa puurti cheyadam dwara apomorphine ghnaapakasakti paniteerunu gananeeyamgaa meruguparustundi.
oligomeric (oo) aβ42 (aβ yokka oka jaathi), karige kanaantara roopamlo, casine kines 2nii sakriyam cheyadam dwara, yaad (daani prarambha dasallo) nuu vargeekarinche pathophysiology ayina synaptic transmissionnu teevramgaa nirodhistundani rendu patraalu choopinchaayi.
inflammatory hypothesis.
medadulo nirantara shotha pratispandana anedi prakatana pathology yokka pradhana savarinche lakshanam anie mariyu prakatana vyaadhikaarakamlo keelaka savarinche karakamga undavacchani converging sakshyam suuchistumdi. prakatana rogula medadulu perigina inflammatory signalling yokka aneka gurtulanu pradarsistaayi. medadulo deerghakaalikamgaa perigina vaapu anedi prakatana yokka prarambha dasalalo amyloid cascadeku keelakamaina bhaagam anie mariyu prakatana yokka taruvaati dasalalo vyaadhi teevratanu penchutundani taapajanaka parikalpana pratipaadistundi. aarogyakaramaina medadulalo aβ untundi mariyu neuronal gaayam nundi kolukovadamlo, sankramana nundi rakshana mariyu rakta-medadu avarodham marammattulo mukhyamaina saareeraka paniteerunu andistundi, ayithe aβ utpatti medadu yokka clearance saamarthyaanni elaa adhigaminchadam praarambhistundo teliyadu mariyu prakatana purogatini praarambhistundi. oka sambhaavya vivarana emitante, medadu yokka nivaasa roganirodhaka kanam microglia sakriyam kaavadaaniki mariyu cytokins anie piluvabade shotha nirodhaka sankethaala anuvulanu sravinchadaaniki aβ kaaranamavutundi, ivi itara sthaanika microglianu niyamistaayi. teevramaina microglial activation, gaayaaniki pratispandanagaa, prayojanakaramgaa untundi mariyu phagocytosis dwara aβ mariyu itara cellular sidhilaalanu clear cheyadaaniki microglianu anumatistundi, deerghakaalikamgaa activate cheyabadina microglia aβ clearancelo taggina saamarthyaanni pradarsistundi. eee taggina abb clearance saamarthyam unnappatikee, activated microglia interleukins 1β mariyu 6 (il-6, il-1β) mariyu tumour necrosis phyaaktar-alfa (tnf-a) vanti proo-inflammatory cytokinlanu sravistuunae undhi, alaage reactive oxygen jaatulu aarogyakaramaina synaptic paniteeruku antaraayam kaliginchi chivariki neuronal maranaaniki kaaranamavutaayi. synaptic paniteeru kolpovadam mariyu taruvaata neuronal maranam anedi abhignaa balaheenatalaku mariyu prakatanatho sambandham unna keelaka medadu praantaalalo valume kolpovadaniki baadhyata vahistundi. ill-1bii, ill-6, mariyu tnf-eah anedi beata oligomerla marinta utpattiki, alaage tou hyperphosphorylationku kaaranamavutaayi, idhi nirantara microglia kriyaaseelataku daariteestundi mariyu feed forward mechanismnu srushtistundi, dheenilo beata utpatti perugutundi mariyu beata clearance taggutundi, idhi chivariki beata falakaalu erpadataaniki kaaranamavutundi.
chaaritraka colinergic parikalpana.
prakatana abhivruddhi yokka colinergic parikalpananu modata 1976loe peater davis mariyu eah.zhe.eff maloney. algimers vyaadhi mukhyamaina neurotransmitter ayina acetylcholine utpattilo lopam kaaranamgaa praarambhamavutundani idhi perkondi. chaalaa prarambha chikitsa parisoedhana eee parikalpanapai aadharapadi undhi, indulo "colinergic nucleus" punaruddharana kooda undhi. eee parikalpana aadhaaramgaa kana-pratyaamnaaya chikitsa yokka sambhaavyatanu parisoedhimchaaru. modati taram anty-algimers mandulannee eee parikalpanapai aadharapadi untaayi mariyu acetylcholinesterase (acetylcholine vichchinnam chese enjaimlu) nuu nirodhinchadam dwara acetylcholine nuu samrakshinchadaaniki panicheestaayi. eee mandulu, konnisaarlu prayojanakaramgaa unnappatikee, nivaaranaku daariteeyaledu. anni sandarbhaallo, vaaru vyaadhi lakshanaalaku matrame chikitsa chesaaru mariyu daanini aapaledu ledhaa tippaledu. eee phalitaalu mariyu itara parisoedhanalu acetylcholine lopaalu neerugaa kaaranamkaanivi kakapovachhu, conny vistrutamaina medadu kanajaala nashtam phalitamgaa, kana-pratyaamnaaya chikitsalu asadhyamga unde vidhamgaa vistrutamgaa debbatinnayani nirdhaaranaku daariteesaayi.
iteevali parisoedhanalu tappugaa madathapette mariyu samagra proteinla prabhavalapai kendrikrutamai unnaayi, amyloid beata mariyu touh tou protein asaadhaaranatalu vyaadhi cascadenu praarambhinchavacchu, appudu beata amyloid niksheepaalu vyaadhini abhivruddhi chestaayi.
glucose viniyogam.
maanava medadu sareeramlo atyanta jeevakriya kriyaaseela avayavaalalo okati mariyu adenosine trifasphate (etipi) roopamlo cellular saktini utpatti cheyadaaniki pedda mottamlo glucosenu jeevakriya chestundi. adhika shakti avasaralu unnappatikee, medadu shakti utpatti kosam uparitalaalanu upayoginchagala saamardhyamlo saapekshamgaa vasyata kaligi untundi mariyu daani shakti avasaraala kosam daadaapu puurtigaa glucose prasaranapai aadhaarapadutundi. glucose sarafara antaraayam kaligithe ledhaa glucose jeevakriya cheyagala saamarthyam lopabhooyishtamgaa maarithe glucose meeda eee aadharapadatam medadunu pramaadamloo padestundi. medadu eah. tii. pii. nii utpatti cheyalekapothe, synapsesnu nirvahinchadam saadhyam kaadu mariyu kanaalu panicheyavu, chivariki ghnaana balaheenataku daariteestundi.
imaging adhyayanalu vyaadhi praarambhamlo algimers vyaadhi rogula medadullo glucose viniyogam tagginatlu choopinchaayi, abhignaa balaheenata yokka clinical sankethaalu sambhavinche mundu. clinical lakshanaalu abhivruddhi chendadamtho mariyu vyaadhi abhivruddhi chendadamtho glucose gvakriyalo eee taggudala marinta teevramavutundi. adhyayanalu algimers vyaadhi unna rogulalo cerebral glucose metabolismlo 17%-24% ksheenatanu kanugonnayi, vayassu-saripolina niyanthranalatho poliste. appati nundi aneka imaging adhyayanalu eee pariseelananu dhruvikarinchayi.
mastishkamlo glucose jeevakriya yokka asadhaaranamgaa takkuva raetlu algimers vyaadhi medadulooni oka lakshana namoonaalo kanipistaayi, mukhyamgaa posterior singulate, parial, temporal mariyu prefrontal cartiseslo. eee medadu praantaalu ghnaapakasakti mariyu ghnaanam yokka bahula amsaalanu niyantristaayani nammutaaru. eee jeevakriya namuunaa punarutpatti cheyadaginadi mariyu algimers vyaadhiki roganirdhaarana saadhanamgaa kooda pratipaadinchabadindi. antekakunda, taggina mastishka glucose jeevakriya (dcgm) marinta adhunaatana vyaadhi unna rogulalo phalaka saandrata mariyu abhignaa lopalatho sambandham kaligi untundi.
taggina mastishka glucose jeevakriya (dcgm) anedi medadu kanaala nashtam yokka kalakhandam matrame kakapovachhu, endukante idhi algimers vyaadhi pramaadam unna lakshanarahita rogulalo sambhavistundi, apolypoprotein ii janyuvu yokka epsilon 4 roopaantaraaniki rogulu sajaateeyamgaa untaaru (apo 4, algimers vyaadhiki janyuparamaina pramaada karakam), alaage algimers vyaadhi yokka vaarasatva roopaalalo. itara clinical mariyu pathological maarpulu sambhavinchadaaniki mundhe dcgm sambhavistundi kabatti, algimers vyaadhiloo gamaninchina sthuula kana nashtam kaaranamgaa idhi jarige avakaasam ledhu.
abhignaa balaheenata sankethaalu laeni yuva vayojana apo 4 vahakalu palgonna imaging adhyayanaalalo, algimers vyaadhi unna paatha vyaktula maadirigaane medadulooni adhe praantaalalo taggina mastishka glucose jeevakriya (dcgm) kanugonabadindi. ayithe, dcgm anedi apo 4 vahakalu matrame kaadu. algimers vyaadhi nirdhaarana ayye samayaniki, genotypelyna apo 3/ii 4, apo 3/ii 3, mariyu apo 4/ii 4 laloe dcgm sambhavistundi. anduvalla, dcgm anedi vyaadhi sthithiki jeevakriya biomarker.
insulin signalling.
gatha dasaabdamloo algimers vyaadhi mariyu madhumeham madhya sambandham sthaapinchabadindi, endukante madhumeham yokka lakshanamaina lakshanam ayina insulin nirodhakata, algimers vyaadhi unna vyaktula medadulalo kooda gamaninchabadindi. neurotoxic oligomeric amyloid-beata jaatulu neuronal kana uparitalampai insulin graahakaala vyakteekarananu taggistaayi mariyu neuronal insulin signalingnu raddu chestaayi. pora lipid micro domainla erpaatulo palgone neuronal gangliosidelu, neuronal uparitalam nundi insulin grahakalanu amyloid-beata-prerita tolagimpunu sulabhataram chestayani soochinchabadindi. algimers vyaadhiloo, oligomeric amyloid-beata jaatulu tnf-α signalingnu prerepistaayi. tnf-α dwara sii-juun enn-terminal kines kriyaaseelata ottidi-sambandhita kineslanu sakriyam chestundi mariyu phalitamgaa irs-1 serin phosphorylationku daariteestundi, idhi taruvaata diguva insulin signalingnu nirodhistundi. phalitamgaa vachhe insulin nirodhakata abhignaa balaheenataku dohadam chestundi. tatphalitamgaa, neuronal insulin sunnitatvam mariyu signalling peragadam anedi algimers vyaadhiki chikitsa cheyadaaniki oka kotta chikitsa vidhanamgaa undavacchu.
aakseekarana ottidi.
aakseekarana ottidi anedi yaad yokka vyaadhikaarakamlo keelaka karakamga udbhavistondi. reactive oxygen jaatulu (aros) adhika utpatti prakatanalo amyloid beata perukupovadam mariyu nikshepanalo keelaka paatra pooshistundani bhaavistunnaaru. prakatana rogula medadulu nuclear mariyu mitochondrial dna rendintiloonuu aakseekarana dna nashtam yokka adhika sthaayilanu kaligi untaayi, ayithe mitochondrial dna nuclear dna kante sumaru 10 retlu ekkuva sthaayilanu kaligi untundi. AD loe neurodegeneration yokka moolamlo vruddhaapya mitochondria keelaka amsam kaavacchu. telikapati abhignaa balaheenata unna vyaktulu, saadhaarana vruddhaapyam mariyu prarambha chittavaikalyam madhya dasha, vaari anhu mariyu mitochondrial medadu DNAloe aakseekarana nashtanni penchaaru (vruddhaapya medadunu chudandi). sahajamgaa sambhavinche dna double-strand viramalu (dsbs) maanava kanaalalo ekkuvagaa reactive oxygen jaatulu, topoisomerases mariyu ushna hecchutaggula kaaranamgaa jalavisleshana vanti vividha prakriyala dwara prerepinchabadina single-strand viraamaala nundi utpannamavutaayi. neuronlalo dsbs anedi memory erpaatu yokka saareeraka prakriyaloo bhaagamgaa rakam II topoisomerase dwara prerepinchabadataayi. prakatana kaani vyaktula kante prakatana rogula postmortem maanava hippocompasloni neuronlu mariyu austrocytelu rendintiloonuu dsbs adhika sthaayilo untaayi. prarambha dasala nundi hippocompus mariyu frontal cartexloni neuronlu mariyu austrocytelalo dsbs perukupovadamto anubandham kaligi untundi. hippocompasloni amyloid phalakaala sameepamlo dsb penchabadutundi, idhi dsb perukupovadamlo ebiti yokka sambhaavya paatranu suuchistumdi ledhaa dheeniki viruddhamgaa untundi. dna double-strand viramalanu marammatu cheyadaaniki pradhana yantraangam naan-homolagus end joining (enhez), idhi dna-dependent protein kines (dna-pike) complexenu upayoginche oka yantraangam. saadhaarana medadulatoe poliste prakatana medadullo dna-pike utpreraka upaghatakam yokka end joining activity mariyu protein sthaayilu gananeeyamgaa takkuvagaa untaayi.
collustroll parikalpana.
collustroll parikalpana anedi amyloid parikalpana, tou parikalpana mariyu sambhaavya shotha parikalpana kalayika. collustroll amyloid mariyu tou utpatti rendinti paiki unnatlu choopabadindi. collustroll austrocyteslo utpatti cheyabadutundi mariyu neuronlaku ravana cheyabadutundi, akkada idhi uparitala pradarsana anie piluvabade prakriya dwara amyloid utpattini sakriyam chestundi. prakriyaku apo avasaram. tou utpatti yokka collustroll niyantrana gurinchi antagaa ardham kaaledu, conny collustroll samslaeshanha enjaim sreb 2 nuu tolaginchadam valla tou phosphorylation taggindi. sahaja roganirodhaka shakti collustroll samshlaeshanhanu prerepistundi mariyu kanaalu collestraalnu teesukuntaayi. bahusha medadulooni oka kanam vruddhaapyamtho maranistundi mariyu idhi sahaja roganirodhaka saktini prerepistundi. medadulooni collustroll samshlaeshanhatoe inflammatory parikalpananu neerugaa mudipettadaaniki marinni adhyayanalu avasaram.
relin parikalpana.
1994loe jarigina oka adhyayanamlo algimers vyaadhiloo isoprenoid maarpulu saadhaarana vruddhaapyamlo sambhavinche vatiki bhinnamgaa untaayani, anduvalla eee vyaadhini akaala vruddhaapya phalitamgaa pariganinchalemani choopinchindi. vruddhaapyamlo maanava medadu dolicol sthaayilalo pragatiseela perugudalanu chooputundi, idhi ubiquinone sthaayilalo taggudala, conny collustroll mariyu dolichil fasfate yokka saapekshamgaa maarani saandratalu. algimers vyaadhiloo, dolicol sthaayilu taggadam mariyu ubiquinone sthaayilu peragadamtho paristhiti tiragabadutundi. collustroll marakunda undagaa, dolichile fasfate saandratalu kooda perugutaayi. chakkera vaahaka dolichile fasfate perugudala vyaadhigrasta medadulo glycosylation raetu peragadaanni mariyu medadunu aakseekarana ottidi nundi rakshinche prayatnamgaa antarjaniya anty-accident ubiquinone perugudalanu pratibimbimchavachchu, udaaharanaku lipid peroxidation dwara prerepinchabadutundi. gatamlo russialo gurtinchabadina ropren, algimers vyaadhi eluka namoonaalo neuroprotective.
pradhanamgaa elukala prayogaala aadhaaramgaa saapekshamgaa iteevali parikalpana algimers vyaadhi prarambhanni pedda extra cellular protein relin yokka hypofunctiontho anusandhaanistundi. vyaadhi saadhaaranamgaa praarambhamayye maanava entorinal cartexlo relin taggudala spashtamgaa kanipistundi, ayithe rogula itara medadu nirmaanaalalo relin sthaayilanu bharti cheyadam kooda nivedinchabadindi. keelaka praamukhyata kaligina, relin yokka athi vyakteekarana algimers vyaadhi namuunaa elukalu mariyu τ-protein atigaa vyakteekarinchae elukala abhignaa saamardhyaalanu rakshistundi. iteevali circuit sthaayi namuunaa relin ksheenata episodic memory prarambha ksheenataku elaa daariteestundo oka yantraamgaanni pratipaadinchindi, tadwara relin parikalpana yokka saiddhaantika punaadi vestundi.
pedda janyu asthirata parikalpana.
2017loe jarigina bioinformatics vislaeshanhaloo chaalaa pedda maanava janyuvulu medadulo gananeeyamgaa ekkuvagaa vyakteekarinchabadataayani mariyu post synaptic nirmaanamloo paalgontaayani velladaindi. eee janyuvulu kana samslaeshanha janyuvu antology (goo) paramgaa kooda baga samruddhiga untaayi mariyu tarachugaa chromosome pelusugaa unde pradaesaalaku mapp chestaayi. amyloid puurvagaami protein (yap) mariyu gaama-sraavam, alaage apo grahakaalu mariyu gwa risk lokeetho sahaa telisina algimers vyaadhi pramaada janyu utpattulu chaalaa varaku ilanti kana samslaeshanha yantraamgaalalo palgontayi. algimers vyaadhi vyaadhikaarakaaniki kanaalu mariyu synaptic samslaeshanha yokka panicheyakapovadam kendramgaa undani, mariyu pedda synaptic samslaeshanha janyuvula utparivartana asthirata anedi nara prasaara antaraayam mariyu medadu vruddhaapyamlo synaptic nashtam yokka kaaranaatmaka trigger kaavacchu anie nirdhaarinchabadindi. oka vilakshanhamaina udaaharanagaa, eee parikalpana daani bhaarii lipoprotein grahakam, lrp1b yokka sanketam sandarbhamlo prakatana yokka apo risk lokasnu vivaristundi, idhi medadu-nirdishta vyakteekaranhatho kuudina pedda kaniti-anachivese janyuvu mariyu asthira chromosome pelusugaa unna pradaesaaniki kooda mapp chestundi. pedda janyu asthirata parikalpana dna nashtam yantraamgaanni algimers vyaadhi pathophysiologyki kendramgaa unchutundi.

