ALZHEIMER

Nama: Dadan Hauri

NIM

: I1021131048

Alzheimers disease (AD) :

an age-related neurodegenerative disease that affects approximately 5 million persons in the US population,
in a few decades more than 14 million individuals will be at risk if either the progression of the disease is not
slowed or a cure is not identied.
AD brain is characterized pathologically by
senile plaques (SP),
neurobrillary tangles (NFT),
synaptic disruption,
mitochondrial oxidative damage
and progressive neuronal decits .

The inammatory processes observed in AD are proposed to involve astrocytes and

microglia. Amyloid- (A) can induce a cascade of cellular mechanisms that includes :

activation of astrocytes, which leads to neuronal damage.

In addition, microglia cells are found to be closely associated with neuritic and A
plaques .

The process of glial activation was characterized by upregulation of molecules such as

cytokines that include: interleukin-1 (IL-1), transforming growth factor- (TGF-),
tumor necrosis factor-a (TNF-a), neurotrophic molecules, various components of
complement proteins and reactive oxy gen species, and neurotoxic products.
Several lines of evidence have shown that the NF-Bin microglia is activated by amyloid . Further, activation of NF-B can stimulate increased expression of TNF-a, IL-1,
IL-6, NOS etc , that could eventually lead to increased modication of the proteins.
However, in the absence of additional research, the exact role of inammation in AD
pathogenesis is unclear.

Further mutations of the genes :

presenilin-1 (PS1),

presenilin-2 (PS-2)
amyloid precursor protein (APP) have been observed in inherited AD.
Moreover, there is also a risk association between AD and genes :
allele 4 of the apolipoprotein E (APOE) gene,
endothelial nitric oxide synthase 3,
alpha-2-macroglobulin
sortilin-related receptor SOLR1 .

Genetics of Alzheimer Disease

There are three genes known to be important in the aetiology
of the early-onset familial condition:
the APP on chromosome 21,
the presenilin-1 (PS1) gene on chromosome 14
the presenilin-2 (PS2) gene on chromosome 1.
Apolipoprotein E on chromosome 19 is an important risk
factor for sporadic Alzheimer disease.

PROSES TERJADI NYA AD

In addition to the formation of SP and NFT,
gliosis,
chronic inammatory reactions,
excitotoxic damage
oxidative stress all appear to contribute to the
progression of AD.
Mutasi missense yang mengubah asam amino tunggal
dan oleh karena itu dikenal adanya tiga jenis gen dalam
satu jalur kekerabatan tertentu memiliki potensi sebagai
pencetus timbulnya Alzheimer

Gb.2 Perubahan Residu Asam Amino pada Suatu

Segmen Protein Prekursor -amyloid Berbatasan
dengan Domain Transmembran Dihasilkan dari Mutasi
Missense dan Menyebabkan Penyakit Alzheimer
Familial Early Onset.Huruf-huruf merupakan kode
asam amino huruf tunggal pada protein prekursor amyloid, dan angka-angka menunjukkan posisi asam amino.
Perubahan residu asam amino dekat dengan sisi pemotongan
-, a-, dan -sekretase (segitiga merah). Residu normal yang
terlibat dalam mutasi missense diperlihatkan sebagai
lingkaran hijau, dimana residu asam amino yang
merepresentasikan berbagai mutasi missense diperlihatkan
dengan kotak kuning. Mutasi menyebabkan akumulasi
peptida A42 toksik dibandingkan peptida wild type A 40

mutasi
yang bertanggung jawab atas
.
pewarisan Alzheimer adalah penyandian
prekursor protein -amyloid pada kromosom
21 dan dua gen yang satu sama lainnya
mirip yaitu presenilin 1 (PSEN1) pada
kromosom 14 dan presenelin 2 (PSEN2) pada
kromosom 1

Mutasi pada PSEN dan APP ditemukan pada pasien

Alzheimer yang disebabkan oleh keturunan menunjukkan
adanya peningkatan produksi A 42 . A merupakan
bahan neurotoksik penyebab Alzheimer secara patogen