2. Folio Biosciences Alzheimer’s Tissue and Biofluids
Capabilities
About:
Alzheimer’s Disease tissue and biofluids are invaluable research material to
understand the underlying physiology of the disease, discover biomarkers,
and test drugs that may potentially retard plaque development, prevent
plaque formation, and treat the progressive degenerative destruction of the
brain.
Folio Biosciences offers quality tissue and biofluids from clinically and
pathologically confirmed Alzheimer’s Diseased donors and Mild Cognitively
Impaired (MCI) donors. Folio certifies the Alzheimer’s pathology and
ensures that the tissue is suitable for gene and protein expression studies. The
diagnosis and classification of Alzheimer’s disease is based on clinical
findings and neuropathology. We use histochemical, immunocytochemical,
and in situ hybridization techniques to ascertain the pathology and RNA
integrity of the Alzheimer’s brain tissue. The brain is diagnosed and qualified
by a board-certified neuropathologist.

3. Alzheimer’s Brain Procurement:
Folio’s extensive partner network allows us to collect Alzheimer’s brains and
normal brains that are matched for age and gender from legally
consented donors. Brains are validated for Alzheimer’s pathology by Folio’s
neuroanatomists and neuropathologists. Each case is linked with extensive
clinical and pathologic information. All brains can be micro-dissected
with regions of the hippocampus laser capture micro-dissected to your
specifications.
Alzheimer’s Bio-fluid Procurement:
Again, Folio’s extensive partner network is leveraged to provide matched
cerebral spinal fluid, plasma, serum, and whole blood from clinically
diagnosed Alzheimer’s and Mildly Cognitively Impaired patients, as well as
Cognitively normal patients. Patients are rigorously screened by board-
certified neurologists with extensive clinical and medical history available.
Biofluids are procured on an on-going basis to serve all your longitudinal
study needs.

4. Available Data:
Brain Clinical: Age, Sex, Race, Comprehensive Medical History, Surgical History,
Medications at time of death, Environmental and Occupational Exposures, Family
History, OB GYN History, and Cause of death. Additionally, MMSE and TICS are scored
several months prior to death and is available for most donors.
Brain Pathology: NIA/Reagan Institute Score, CERAD score, ADRDA/Khachaturian
score, Braak score, Quantification of Neuritic and Diffuse Plaques, Brain Weight, and
Autolysis.
Biofluids Clinical: Age, Sex, Race, Years of Education completed, Marital Status,
Comprehensive Medical History, Surgical History, Medications at time of collection,
Environmental and Occupational Exposures, Family History, OB GYN History. MMSE,
CDR, and ADL assessments are performed every six months by a board certified
neurologist.
Control Specimens: Control subjects self-reported no history of neurological disease;
the great majority had Mini-Mental State Exam (MMSE) data indicating no cognitive
impairment; a subset of these subjects have had a full neurological work-up.
Imaging: PET and MRI imaging scans are available from Alzheimer’s and Mildly
Cognitively Impaired bio fluid donors.

5. Longitudinal Studies:
Created and priced on a case by case basis, Folio recruits, clinically
characterizes and longitudinally follows individuals with Alzheimer disease, Mild
Cognitive Impairment (MCI ), other dementias and healthy controls. Studies
can be designed as prospective procurement following a subject for a short
monthly period of time or yearly all the way to autopsy.
In addition, Folio has access to a longitudinal relational research database that
currently holds data for over 4,000 research subjects with an average of 5
evaluations each. 1,503 research subjects have 4 or more evaluations and the
maximum number of evaluations per subject is 37.

6. Sample Longitudinal Study
Data Collected 24 cases of AD to include:
Gender CSF - IGG Levels
APOE Status Serum IGG
Baseline 3 months 12 Months
Blood Pressure Intracranial Volume
BMI VentricularVolume
2mls CSF, 2 mls of 2mls CSF, 2 mls of 2mls CSF, 2 mls of
MMSE Hippocampal Volume serum and/or serum and/or serum and/or
Temporal Lobe Volume plasma, plasma, plasma,
CDR
neuropsychological neuropsychological, neuropsychological,
CSF Albumin Total Brain Volume , blood chemistry blood chemistry blood chemistry
White Matter Hypersensitivies data imaging data, data , imaging data and imaging
BLOOD Albumin
genetic data data, genetic data data, genetic data
Hachinski Ischemia Scores

7. Folio’s Neuroscience Capabilities: Brain Tissue
Tissue Preparations:
•Fresh quick-frozen tissue blocks or coronal sections (nitrogen vapor or dry ice frozen)
•Passive frozen hemispheres (Dissection of specific anatomic regions)
•Formalin-fixed hemispheres (specific anatomic regions)
Fixed Tissue Protocol
Flash Freezing Protocol right mid frontal gyru
Midfrontal gyrus left mid frontal gyrus
Inferior parietal lobule frontal lobe white matter (1cm anterior to lat vent)
Posterior superior temporal gyrus right inferior parietal lobule
Primary visual cortex left inferior parietal lobule
Hippocampus (rostral to caudal) right superior and middle temporal gyrus
Amygdala left superior and middle temporal gyrus
Putamen (1 precommissural, 1 at anterior anterior cingulate gyrus
commissure, 1 postcommissural) right primary visual cortex
Globus pallidus (1 precommissural, 1 at left primary visual cortex
anterior commissure, 1 postcommissural) hippocampus at level of uncus
Caudate (1 precommissural, 1 at anterior hippocampus at the level of the lateral geniculate
commissure, 1 postcommissural) amygdala right
Midbrain (rostral to caudal) striatum at the level of the anterior commissure
Pons (rostral to caudal with first including left striatum at the level of the anterior commissure
the locus ceruleus) right thalamus
Medulla (rostral to caudal) left thalamus
Cerebellar cortex midbrain with substantia nigra
pons
medulla
cerebellar cortex
spinal cord/pituitary (as available)

8. Tissue Preparations:
Frozen Tissue: Over 450 autopsy brains including AD, PD, tauopathy, Huntington's
disease, Multiple Sclerosis, Schizophrenia, other neurodegenerative diseases, and
controls. The fresh quick-frozen specimens are optimally preserved with minimal ice
artifact formation. These specimens are suitable for the widest variety of applications,
including receptor binding, immunocytochemistry, in situ hybridization, virus detection,
polymerase chain reaction (PCR), DNA sequencing, mRNA isolation, and certain
neurochemical assays. Micro-dissections can be performed before freezing or after
freezing by laser capture micro-dissection by qualified neuro-anatomists.
Brain Biopsies: ~30 frozen specimens and ~50 paraffin blocks including AD, PD collected
during pallidotomy surgery, tauopathy, Creutzfeldt-Jakob disease, and other diagnoses
Formalin Fixed Tissue: Over 400 cases of AD, PD, tauopathy, Huntington's disease,
Multiple Sclerosis, Schizophrenia, and Paraffin Blocks from other neurodegenerative
diseases, and controls
Paraformaldehyde-fixed Tissue: Paraffin Blocks of AD, PD and other neurodegenerative
diseases, and controls
Cryopreserved Tissue: Over 2,000 cases of AD and thousands of PD, tauopathy,
Huntington's disease, Multiple Sclerosis, Schizophrenia, and other neurological and
psychiatric conditions

9. Diagnosis Number Percentage
Control ** 1401 22%
Possible Alzheimer’s Disease 250 4%
Probably Alzheimer’s Disease 1000 16%
Mild Cognitive Impairment (MCI) 329 5%
Frontoemporal dementia (FTD) 155 2%
Vascular dementia 59 1%
Other dementia 42 1%
Lewybody Disease (LBD) 75 1%
Parkinson’s disease 607 9%

10. Diagnosis Number Percentage
Control ** 1401 22%
Possible Alzheimer’s Disease 250 4%
Probably Alzheimer’s Disease 1000 16%
Mild Cognitive Impairment (MCI) 329 5%
Frontoemporal dementia (FTD) 155 2%
Vascular dementia 59 1%
Other dementia 42 1%
Lewybody Disease (LBD) 75 1%
Parkinson’s disease 607 9%