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Alzheimer's Disease (Science) > Everything (Week 3) > Flashcards

Everything (Week 3) Flashcards

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Biology 101 flashcards
1
Q

AlzeCure

A

ACD855 (NeuroRestore) - entering Phase 1 and ACD679 (Alzstatin) and AC25793 (steroid derivative that is a positive modulator of TrkA and TrkB for AD) - both preclinical

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2
Q

How does sleep/wake changes relate to abeta and tau? What about sleep deprivation?

A

Sleep/wake cause changes in neuronal activity/metabolism which seems to regulate abeta and tau level spreading in ISF. After sleep deprivation, tau increases by 40%, but no other proteins like NF-L or GFAP

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3
Q

What are the two ways to puff up income statement?

A
  1. Improperly increase revenue (usually by moving to different periods)
  2. Improperly lowered costs or expenses (Shifting between periods, making depreciation lower, probable liabilities not accrued, operating losses masked in discontinued operations)
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4
Q

What will Eisai trial use as primary endpoint for Phase 3?

A

CDR-SB

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5
Q

Sangamo programs

A

Many other programs, lead program is Hemophelia B in Phase 1/2; AAV-tauopathy program preclinical, ALS program partnered with Roche, HD partnered with Shire (both in research stages)

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6
Q

What is DARC? What clinical trials is it in?

A

Detecting apoptotic retinal cells - Injecting fluorescently labeled Annexin V dye into arm to label apoptosis to be taken up into retina. Phase 2 for Glaucoma, AMD, and AD

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7
Q

What is equation for Cash flow forcasting?

A

Total cash flow = Cash flow from operations (+Depreciation - Taxes) - Capital spending - Increase in Working Capital

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8
Q

What is NPV used for?

A

It is a good way to compare multiple different projects in a standardized way; it is a direct measure of expected value added to the company from executing the capital project

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9
Q

How does IRS-1 pS relate to cognitive dysfunction in AD?

A

IRS-1 pS abnormalities correlate with cognitive dysfunction independent of abeta and tau.

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10
Q

What is discount rate? What is another name?

A

Used to calculate NPV, like interest, but in reverse. Sometimes called the “hurdle rate” - company’s minimum acceptable return

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11
Q

What are the other prevention trials happening WW like FINGER? (5)

A

US-Pointer, UK-Finger, Maintain your brain - Australia, SINGER - Singapore, MIND FINGER - China

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12
Q

What is present value?

A

Calculations used to compare cash flows (cash spent and received) at different times in the future.

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13
Q

When was the last common ancestor of humans and chimpanzees?

A

7M years ago

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14
Q

What is the agent injected to look at BBB breakdown, what technique is utilized?

A

Gadolinium tracer; DCE-MRI (Dynamic contrast enhanced)

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15
Q

What is the FINGER study? What 4 interventions? What were the results?

A

FINGER is a 2 year longitudinal study testing lifestyle changes trying to prevent cognitive decline in at-risk elderly people testing diet, exercise, cognitive training, and vascular monitoring; also included a 5-7 year follow up study. 70% did all 4 interventions - showed 25% reduction on NTB and 30% lower risk for functional decline (AIDL) at 24 months (not segmented for abeta)

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16
Q

What is ADCOMS?

A

6 items of CDR-SB, 4 items of ADAS-Cog, 2 items of MMSE

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17
Q

In order to be safe, what do vaccines need to avoid?

A

Activation of autoreactive T-cells in the periphery

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18
Q

What is Abeta/Calpains/TrkB pathway?

A

Abeta leads to increased intracellular Ca which activates calpains which cleave TrkB into TrkB-T’ and TrkB-ICD to not allow for BDNF signaling

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19
Q

What is “Cost of equity capital”? WACC?

A

Expected return for VCs and interest rate for banks
WACC - Weighted average cost of capital - sum of individual percent ownership multiples by cost of equity to get expected average return. This can be used as benchmark to determine minimum future growth - sued as discount rate in NPV analysis

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20
Q

What are values measured in? What are examples (5)? What can it be measure in (2)?

A

Values are measured in currency.
PV, FV, Discounted value, terminal value, NPV
Nominal dollars (actual money) vs. real dollars (adjusted for inflation)

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21
Q

Alzemend Neuro

A

Therapeutic vaccine for AD (targeting immune response -dendritic cells); LiPoSal (Lithium, Proline, Salycylate) - leveraging cocrystal tech for AD

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22
Q

What are rates measured in? Give 4 examples and 3 specialized examples

A

Rates are measured in percentages and are associated with a time period.
Inflation rate, discount rate, hurdle rate, interest rate
Internal rate of return, return on investment, risk premium

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23
Q

What are the two ways to “cook the books” of the financial statements?

A

Usually affecting income statement or balance sheet.

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24
Q

At 90, what is relationship between AD pathology and dementia?

A

60% have AD pathology and dementia, 42% have AD pathology and no dementia - resilient or preclinical AD?

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25
Q

What 5 things need to happen for revenue to be appropriately recorded?

A
  1. An order has been received
  2. The actual product has been shipped.
  3. There is little risk the customer will not accept the product
  4. No significant additional actions are required by the company
  5. Title has transferred and the purchaser recognizes his responsibility to pay
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26
Q

When is interest tax deductible?

A

Interest is tax deductible as a business expense (effective cost of capital is lowered by the 34% expected tax savings) Ex: 10% interest x 66% = 6.6% cost of equity capital

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27
Q

What negative effects can growth factors have? How can you circumvent these?

A

Growth factors can cause toxic off target effects so need to inject locally.

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28
Q

What is discounting?

A

Discounting - process of finding the present value today of cash to be received at some future date.

29
Q

What actin modulator is reduced in AD and what processes does it effect (2), what happens in aged neurons?

A

CD2AP is reduced in AD - reduces actin and increases APP processing in endocytic trafficking; neuronal aging increases APP endosomal uptake

30
Q

Debt financing from banks? How do banks set interest rate?

A

“Risk free” + “Risk premium” interest rate
Risk free - lending return from government bonds
Risk premium - based on how risky they determine the business to be

31
Q

What PET agent can detect microvascular changes and when can it be detected in AD patients?

A

18F-V45 - measures microvascular perfusion and can be detected early in AD (before FDG-PET)

32
Q

What is normal level of antibody concentration into the brain from the periphery?

A

0.1-0.2%

33
Q

What clinical trials using growth factors have been and are being tested in AD?

A

Cere-110 AAV-NGF was injected into the basal cholinergic region in Phase 1 and Phase 2 - had no clinical benefit, but also wasn’t localized (was partnered with Sangamo, but dropped partnership in 2015). New Phase 1 using AAV-BNDF to begin in early 2019 in early AD and MCI to be injected in entorhinal cortex and hippocampus.

34
Q

Internal rate of return (IRR)

A

Discount rate at which NPV = $0 (present value of future cash flow = initial investment)

35
Q

What are the 4 Ts that matter for Type 1 behavior?

A

Autonomy of time, tasks, team, and techniques

36
Q

What is CAA? What 2 characteristics?

A

Cerebral amyloid angiopathy - characterized by amyloid beta in blood vessels in the brain; represent as microvascular lesions (microbleeds and microinfarcts)

37
Q

How many cases of AD can be prevented by lifestyle changes?

A

30%

38
Q

Area 10 (8 functions)

A

Area in the lateral prefrontal cortex that is almost 2x bigger in humans than primates; Involved in planning, memory, abstract thinking, cognitive flexibility, initiating appropriate behavior, inhibiting inappropriate behavior, learning rules, picking out relevant information from what is perceived by the senses

39
Q

What is VCID?

A

Vascular cognitive impairment in dementia

40
Q

Polyglutamylated Abeta causes what functional change in mouse model?

A

Motor defects

41
Q

What are 3 innate psychological needs?

A
  1. Autonomy
  2. Competence
  3. Relatedness
42
Q

Casava Sciences

A

New name of Pain Therapeutics - lead compound (PT-125) modulating filamen A for AD

43
Q

What is a proforma financial statement, what does it show?

A

Formatted like a historical financial statement, a proforma shows future financial operations of the company; answers “what might our financial future look like if we make this investment?”

44
Q

What is relationship of Abeta and TLR2 in AD?

A

Abeta can induce TLR2 which leads to inflammation and secretion of TNFa, IL-6, and iNOS

45
Q

When was the last common ancestor of monkeys and apes?

A

25M years ago

46
Q

Capital budgeting

A

The requirement of capital of a business and the return of capital for a business

47
Q

Priavoid (2019)

A

D-peptide programs targeting Abeta oligomers in AD (currently in Phase 1), Neuron-specific Ca channels in neuropathic pain (IND-enabling), reduction of neuroinflammation in ALS (Poc in animals) and a number of development programs (SOD-1 stabilization in ALS, tau oligomers in tauopathies, polyQ in HD, alpha-syn in PD)

48
Q

How does APOE4 affect MAPK signaling? What 2 functional processes does this effect?

A

APOE4>APOE3>APOE2 at inducing MAPK signaling which induces APP synthesis and synaptogenesis by a mechanism dependent on different transcription factors

49
Q

What is the smallest detectable Abeta oligomer form found in solution?

A

Abeta42 pentamers/hexamers

50
Q

2 Methods to sweeten the balance sheet?

A
  1. Improperly increased or shifted period income

2. Improperly increased assets or equity

51
Q

How does discount rate affect NPV value?

A

NPV is lower when discount rate is higher (because computed value of future cash flow is lower if discounted more) and NPV is higher when discount rate is lower

52
Q

Equation for Future Value

A

FV = PV * (1+i)^y (where i is interest and y is years)

53
Q

What is Archer Pharmaceuticals?

A

Nivaldipine (dihydroxypyridine)- Ca Channel blocker that failed Phase 3, but had effect in subset of patients after post hoc analysis.

54
Q

NPV (definition and equation) - what does higher and lower number mean?

A

NPV = -Co + Sum(1 to n years){Cy/(1+d)^y} where Co is initial investment and Cy is net cash flow (cash input - cash output for year y); NPV is value that will be added to a business after converting all future cash inflows and outflows into present value; if NPV is positive - add that value to the business, if negative - project should not be pursued.

55
Q

Describe microbleeds and microinfarcts relation to abeta.

A

Microbleeds - absence of abeta in ruptured vessels, vascular remodeling in unruptured vessels (fibrinogen deposits; Microinfarcts - presence of abeta, stiff vessels involved in this process.

56
Q

What are the 2 retinal layers that change in AD? How do they change?

A

Thinning of the macular retinal nerve fiber layer and retinal ganglion cells. Thicker retinal nerve fiber layer is seen during amnestic MCI (maybe due to gliosis) and then thinning is seen in later stages

57
Q

What does Type 1 behavior depend on (3)?

A
  1. Autonomy
  2. Mastery
  3. Purpose
58
Q

Equation for Present Value

A

PV = FV/(1+d)^y (where d is discount rate per year and y is years)

59
Q

3 Reasons why a dollar today is worth more than tomorrow.

A
  1. Inflation
  2. Risk
  3. Opportunity cost
60
Q

APOE stimulation of kinases is dependent on what factor? What 2 forms of APOE4 are shown to be sufficient to do this?

A

Binding of LDL receptor family members. Physiologically produced APOE in human blood lipoproteins or secreted from glia

61
Q

What are pathway components of APOE (rank order) in affecting APP synthesis and synaptogenesis?

A

APOE4>APOE3>APOE2 -> DLK -> MKK7 -> ERK -> c-fos mediated APP transcription and AP-1 binding site and CREB-mediated synaptogenesis

62
Q

What is the risk of getting AD after 90? What two things are protective after 80 years old?

A

18% (doubling risk after 90), Hypertension and high cholesterol are protective against dementia after 80.

63
Q

What are the 3 laws of mastery?

A
  1. Mastery is a mindset
  2. Mastery is a pain
  3. Mastery is an asymptote
64
Q

Where does expression of TLR4 and TLR9 change in APP/PS1 and APPKI mouse models?

A

TLR4 and TLR9 cell surface and endosomal receptors are downregulated in AD

65
Q

How many sets of books should a company have?

A

3

  1. One complete set of books for outside world and to owners of the business
  2. Focused on determining and defending tax liabilities
  3. Other special presentation formats for management to use to control business operations
66
Q

What are differences of microglia in mice vs. human? (3)

A
  1. May more reflect healthy response of microglia
  2. Different responses to oligomeric abeta
  3. Mouse neurons do not degenerate.
67
Q

How does insulin regulated by neurons?

A

Insulin does not have main effect for glucose uptake into neurons; does facilitate glucose signaling and insulin regulates expression and localization of ion channels including GABA, NMDA, and AMPA receptors

68
Q

What is the range of age of onset in an FAD patient?

A

20-70 years old

69
Q

What are the 4 types of apes?

A

Chimpanzees, Gorillas, Orangutans, Gibbons

Alzheimer's Disease (Science) (5 decks)

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