Neurodegenerative disease can cause different symptoms, due to the different region of degradation

Alzheimer's disease¶

Alzheimer’s disease (AD) is defined by brain deposition of numerous amyloid plaques and neurofibrillary tangles. - Mainly due to two type of disordered misfolded proteins - Tau: neurofibrillary - Amyloid plaques (Amyloid $\beta, A\beta$) - Symptoms: - Memory loss - Disorientation in time and space - Difficulty in interpreting images and distances - Poor judgement - Lack of engagement at work and social activities - Problems in oral and written expression - Changes of humor and personality - Also contains varaible clinical subtypes: - Memory syndrome: typical AD - Language syndrome: logogenic variant of AD - Visual syndrome: Posterior variant of AD - Frontal syndrome: frontal varaint of AD

Phases of amyloid-$\beta$ deposition in AD
- no AD or non-AD dementia --> pre_AD dementia --> symptomatic AD
==Braak stages==

Tau: microtubule-associated protein¶

there are six isoforms of tau
The formation of tau neurofibrillary tangels
- Tau 主要和磷酸化有关，会导致microtubule的聚集

AD's biomarkers¶

1. PET: Positron emission¶

PET is a non-invasive imaging tech
using radioactive compounds that bind fibrillary Aβ or tau.

2. Cerebrospinal Fluid (CSF) biomarkers¶

CSF is collected via lumbar puncture and provides direct insight into brain biochemistry:

Amyloid-β42: Decreases in CSF as it accumulates in brain plaques
Total tau and phosphorylated tau: Increase with neuronal damage and tangle formation
Aβ42/Aβ40 ratio: Improves diagnostic accuracy over Aβ42 alone
Neurofilament light chain (NfL): Indicates neuronal damage (though not specific to AD)

3. Blood biomarkers¶

Recent advances have enabled less invasive blood tests:

Plasma p-tau181 and p-tau217: Highly specific for AD pathology
Plasma Aβ42/Aβ40 ratio: Correlates with brain amyloid burden
Plasma NfL: Reflects neurodegeneration but isn't AD-specific
GFAP (Glial Fibrillary Acidic Protein): Indicates astrocytic activation