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INTRODUCTION
Table 1: Major biomarkers used in Alzheimer's disease diagnosis.
|
Biomarker |
Type |
Clinical significance |
Limitations |
|---|---|---|---|
|
Amyloid-β (Aβ42, Aβ42/Aβ40 ratio) |
Amyloid biomarker |
Detects amyloid plaque deposition; useful for early diagnosis |
Can be abnormal years Before symptoms; Limited disease severity correlation |
|
Total Tau (t-tau) |
Neurodegeneration biomarker |
Indicates neuronal injury and degeneration |
Elevated in Multiple Neurological disorders; low specificity |
|
Phosphorylated Tau (p-tau181, p-tau217, p-tau231) |
Tau pathology biomarker |
Highly associated with neurofibrillary tangles; improves diagnostic accuracy |
May vary across assays and clinical settings |
|
Neurofilament Light Chain (NfL) |
Neurodegeneration biomarker |
Reflects axonal damage and disease progression |
Increased in Several Neurodegenerative diseases, not specific to Alzheimer's |
|
Glial Fibrillary Acidic Protein (GFAP) |
Neuroinflammation biomarker |
Indicates astrocyte activation and early pathological changes |
Can increase in other brain disorders and injuries |
|
YKL-40 |
Neuroinflammation biomarker |
Associated with Glial activation and inflammatory response |
Limited specificity and routine clinical use |
|
Neurogranin |
Synaptic dysfunction biomarker |
Reflects synaptic loss and cognitive decline |
Mostly measured in CSF; limited standardization |
|
Brain atrophy (hippocampal volume loss) |
Imaging biomarker |
Shows structural brain changes related to disease progression |
Atrophy may occur in normal aging and other dementias |
|
Reduced Glucose Metabolism (FDG-PET) |
Functional imaging biomarker |
Detects Reduced brain metabolic activity |
High cost and limited availability |
|
α-Synuclein |
Associated biomarker |
Helps identify overlapping neurodegenerative processes |
Not specific for Alzheimer's disease |

Figure 1: Overview of Alzheimer's disease progression and diagnostic pathway.

Figure 2: Major molecular mechanisms involved in Alzheimer's disease pathology.
CURRENT CHALLENGES AND LIMITATIONS
Table 2: Comparison of neuroimaging techniques for Alzheimer's disease diagnosis.
|
Technique |
Advantages |
Disadvantages |
Diagnostic accuracy |
|---|---|---|---|
|
Magnetic Resonance Imaging (MRI) |
Non-invasive; provides detailed structural brain images; detects hippocampal atrophy |
Expensive; Structural changes may appear later in disease progression |
Moderate to high |
|
Computed Tomography (CT scan) |
Widely available; quick imaging process; lower cost than MRI |
Lower sensitivity for early Alzheimer's changes; radiation exposure |
Moderate |
|
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) |
Detects reduced glucose metabolism and functional abnormalities before structural changes |
High cost; Limited accessibility; radiation exposure |
High |
|
Amyloid PET |
Detects amyloid plaque accumulation in early disease stages |
Expensive; amyloid deposits may exist without symptoms |
High |
|
Tau PET |
Direct visualization of tau pathology; useful for disease staging |
Limited availability; costly procedure |
High |
|
Single-Photon Emission Computed Tomography (SPECT) |
Measures Cerebral blood flow; relatively lower cost than PET |
Lower Spatial Resolution and sensitivity |
Moderate |

Figure 3: Workflow of AI-based Alzheimer diagnosis system.
FUTURE PERSPECTIVES

Figure 4: Future direction of AI-assisted Alzheimer's disease management.

